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Sample records for amphiphilic short peptides

  1. Dynamic stability of nano-fibers self-assembled from short amphiphilic A6D peptides

    Science.gov (United States)

    Nikoofard, Narges; Maghsoodi, Fahimeh

    2018-04-01

    Self-assembly of A6D amphiphilic peptides in explicit water is studied by using coarse-grained molecular dynamics simulations. It is observed that the self-assembly of randomly distributed A6D peptides leads to the formation of a network of nano-fibers. Two other simulations with cylindrical nano-fibers as the initial configuration show the dynamic stability of the self-assembled nano-fibers. As a striking feature, notable fluctuations occur along the axes of the nano-fibers. Depending on the number of peptides per unit length of the nano-fiber, flat-shaped bulges or spiral shapes along the nano-fiber axis are observed at the fluctuations. Analysis of the particle distribution around the nano-fiber indicates that the hydrophobic core and the hydrophilic shell of the nano-structure are preserved in both simulations. The size of the deformations and their correlation times are different in the two simulations. This study gives new insights into the dynamics of the self-assembled nano-structures of short amphiphilic peptides.

  2. Short Synthetic α-Helical-Forming Peptide Amphiphiles for Fungal Keratitis Treatment In Vivo.

    Science.gov (United States)

    Wu, Hong; Liu, Shaoqiong; Wiradharma, Nikken; Ong, Zhan Yuin; Li, Yan; Yang, Yi Yan; Ying, Jackie Y

    2017-03-01

    The emergence of fungal keratitis is on the rise globally. However, current antifungal therapeutics are ineffective in severe keratomycosis. Previously reported α-helical peptides comprising 8-14 amino acids demonstrate broad-spectrum antimicrobial activity both in vitro and in vivo. Here, α-helical peptides of the optimized sequences are investigated for antifungal biofilm in vitro and in vivo using a fungal biofilm-caused mouse keratitis model. The peptides with the optimal composition demonstrate higher α-helical propensity and improve antifungal activity in dispersing Candida albicans biofilm in vitro. Moreover, the optimized α-helical peptides are not only effective in treating C. albicans biofilm-induced keratitis in mice, they are also nontoxic to the mice eyes. These peptides have the potential to be developed as antifungal agents for the treatment of C. albicans biofilm-caused keratitis. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Peptide amphiphile self-assembly

    Science.gov (United States)

    Iscen, Aysenur; Schatz, George C.

    2017-08-01

    Self-assembly is a process whereby molecules organize into structures with hierarchical order and complexity, often leading to functional materials. Biomolecules such as peptides, lipids and DNA are frequently involved in self-assembly, and this leads to materials of interest for a wide variety of applications in biomedicine, photonics, electronics, mechanics, etc. The diversity of structures and functions that can be produced provides motivation for developing theoretical models that can be used for a molecular-level description of these materials. Here we overview recently developed computational methods for modeling the self-assembly of peptide amphiphiles (PA) into supramolecular structures that form cylindrical nanoscale fibers using molecular-dynamics simulations. Both all-atom and coarse-grained force field methods are described, and we emphasize how these calculations contribute insight into fiber structure, including the importance of β-sheet formation. We show that the temperature at which self-assembly takes place affects the conformations of PA chains, resulting in cylindrical nanofibers with higher β-sheet content as temperature increases. We also present a new high-density PA model that shows long network formation of β-sheets along the long axis of the fiber, a result that correlates with some experiments. The β-sheet network is mostly helical in nature which helps to maintain strong interactions between the PAs both radially and longitudinally. Contribution to Focus Issue Self-assemblies of Inorganic and Organic Nanomaterials edited by Marie-Paule Pileni.

  4. Self-assembly of fibronectin mimetic peptide-amphiphile nanofibers

    Science.gov (United States)

    Rexeisen, Emilie Lynn

    Many therapeutic strategies incorporate peptides into their designs to mimic the natural protein ligands found in vivo. A few examples are the short peptide sequences RGD and PHSRN that mimic the primary and synergy-binding domains of the extracellular matrix protein, fibronectin, which is recognized by the cell surface receptor, alpha5beta 1 integrin. Even though scaffold modification with biomimetic peptides remains one of the most promising approaches for tissue engineering, the use of these peptides in therapeutic tissue-engineered products and drug delivery systems available on the commercial market is limited because the peptides are not easily able to mimic the natural protein. The design of a peptide that can effectively target the alpha5beta1 integrin would greatly increase biomimetic scaffold therapeutic potential. A novel peptide containing both the RGD primary binding domain and PHSRN synergy-binding domain for fibronectin joined with the appropriate linker should bind alpha 5beta1 integrin more efficiently and lead to greater cell adhesion over RGD alone. Several fibronectin mimetic peptides were designed and coupled to dialkyl hydrocarbon tails to make peptide-amphiphiles. The peptides contained different linkers connecting the two binding domains and different spacers separating the hydrophobic tails from the hydrophilic headgroups. The peptide-amphiphiles were deposited on mica substrates using the Langmuir-Blodgett technique. Langmuir isotherms indicated that the peptide-amphiphiles that contained higher numbers of serine residues formed a more tightly packed monolayer, but the increased number of serines also made transferring the amphiphiles to the mica substrate more difficult. Atomic force microscopy (AFM) images of the bilayers showed that the headgroups might be bent, forming small divots in the surface. These divots may help expose the PHSRN synergy-binding domain. Parallel studies undertaken by fellow group members showed that human

  5. Cellular recognition of synthetic peptide amphiphiles in supported bioartificial membranes

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    Pakalns, Teika

    The goal of this study was to demonstrate that lipidated cell adhesion peptides could form well-ordered biomimetic surfaces that were capable of influencing cellular behavior in a controlled and specific manner. The first step taken was to covalently link synthetic dialkyl tails to the amino-termini of the collagen-derived peptide IV-H1 (amino acid sequence GVKGDKGNPGWPGAP) and the well-known tripeptide Arg-Gly-Asp (RGD) to produce amino-coupled peptide amphiphiles. Other spatial orientations of RGD were also generated by coupling tails to the carboxyl-terminus to give carboxyl-coupled RGD amphiphiles and to both the amino- and carboxyl-termini to give looped RGD amphiphiles. The next step taken was to let the peptide amphiphile self-assemble along with methyl ester-capped dialkyl tails into mixed films. It was found that all the peptide amphiphiles formed stable monolayers at the air-water interface in a Langmuir trough. IV-H1 amphiphiles and carboxyl-coupled and looped RGD amphiphiles deposited well as Langmuir-Blodgett mixed films on solid surfaces at all peptide concentrations, but aminocoupled RGD amphiphiles did not deposit well at high RGD concentrations. FT-IR studies of films containing RGD amphiphiles showed that amino-coupled RGD head groups formed the strongest lateral hydrogen bonds. The final step was to study cellular response to mixed films containing IV-H1 or RGD amphiphiles. The spreading of melanoma cells was influenced by both the molar concentration and spatial orientation of the amphiphilic peptides. Cells spread on IV-H1 and looped RGD films in a concentration-dependent manner, but spread indiscriminately on carboxyl-coupled RGD films and did not spread at all on well-deposited amino-coupled RGD films. The specificity of the cellular response to looped RGD amphiphiles was investigated. Control films of looped Arg-Gly-Glu (RGE) amphiphiles inhibited the adhesion and spreading of melanoma and endothelial cells, and antibody inhibition of the

  6. Drug release from hydrazone-containing peptide amphiphiles

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    Matson, John B.; Stupp, Samuel I.

    2011-01-01

    Hydrolytically-labile hydrazones in peptide amphiphiles were studied as degradable tethers for drug release from nanofiber gels. On-resin addition of the novel compound tri-Bochydrazido adipic acid to a lysine ε-amine allowed for precise placement of a hydrazide in a peptide sequence. Hydrazone formation and hydrolysis were examined by addition and release of nabumetone froma peptide amphiphilematrix.

  7. Drug release from hydrazone-containing peptide amphiphiles.

    Science.gov (United States)

    Matson, John B; Stupp, Samuel I

    2011-07-28

    Hydrolytically-labile hydrazones in peptide amphiphiles were studied as degradable tethers for release of the drug nabumetone from nanofiber gels. On-resin addition of the novel compound tri-Boc-hydrazido adipic acid to a lysine ε-amine allowed for precise placement of a hydrazide in a peptide sequence.

  8. Synthetic cationic amphiphilic α-helical peptides as antimicrobial agents.

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    Wiradharma, Nikken; Khoe, Ulung; Hauser, Charlotte A E; Seow, See Voon; Zhang, Shuguang; Yang, Yi-Yan

    2011-03-01

    Antimicrobial peptides (AMPs) secreted by the innate immune system are prevalent as the effective first-line of defense to overcome recurring microbial invasions. They have been widely accepted as the blueprints for the development of new antimicrobial agents for the treatment of drug resistant infections. However, there is also a growing concern that AMPs with a sequence that is too close to the host organism's AMP may inevitably compromise its own natural defense. In this study, we design a series of synthetic (non-natural) short α-helical AMPs to expand the arsenal of the AMP families and to gain further insights on their antimicrobial activities. These cationic and amphiphilic peptides have a general sequence of (XXYY)(n) (X: hydrophobic residue, Y: cationic residue, and n: the number of repeat units), and are designed to mimic the folding behavior of the naturally-occurring α-helical AMPs. The synthetic α-helical AMPs with 3 repeat units, (FFRR)(3), (LLRR)(3), and (LLKK)(3), are found to be more selective towards microbial cells than rat red blood cells, with minimum inhibitory concentration (MIC) values that are more than 10 times lower than their 50% hemolytic concentrations (HC(50)). They are effective against Gram-positive B. subtilis and yeast C. albicans; and the studies using scanning electron microscopy (SEM) have elucidated that these peptides possess membrane-lytic activities against microbial cells. Furthermore, non-specific immune stimulation assays of a typical peptide shows negligible IFN-α, IFN-γ, and TNF-α inductions in human peripheral blood mononuclear cells, which implies additional safety aspects of the peptide for both systemic and topical use. Therefore, the peptides designed in this study can be promising antimicrobial agents against the frequently-encountered Gram-positive bacteria- or yeast-induced infections. Copyright © 2010 Elsevier Ltd. All rights reserved.

  9. Drug release from hydrazone-containing peptide amphiphiles

    Science.gov (United States)

    Matson, John B.; Stupp, Samuel I.

    2012-01-01

    Hydrolytically-labile hydrazones in peptide amphiphiles were studied as degradable tethers for drug release from nanofiber gels. On-resin addition of the novel compound tri-Bochydrazido adipic acid to a lysine ε-amine allowed for precise placement of a hydrazide in a peptide sequence. Hydrazone formation and hydrolysis were examined by addition and release of nabumetone froma peptide amphiphilematrix. PMID:21674107

  10. Cathepsin-Mediated Cleavage of Peptides from Peptide Amphiphiles Leads to Enhanced Intracellular Peptide Accumulation

    Energy Technology Data Exchange (ETDEWEB)

    Acar, Handan [Institute; Department; Samaeekia, Ravand [Institute; Department; Schnorenberg, Mathew R. [Institute; Department; Medical; Sasmal, Dibyendu K. [Institute; Huang, Jun [Institute; Tirrell, Matthew V. [Institute; Institute; LaBelle, James L. [Department

    2017-08-24

    Peptides synthesized in the likeness of their native interaction domain(s) are natural choices to target protein protein interactions (PPIs) due to their fidelity of orthostatic contact points between binding partners. Despite therapeutic promise, intracellular delivery of biofunctional peptides at concentrations necessary for efficacy remains a formidable challenge. Peptide amphiphiles (PAs) provide a facile method of intracellular delivery and stabilization of bioactive peptides. PAs consisting of biofunctional peptide headgroups linked to hydrophobic alkyl lipid-like tails prevent peptide hydrolysis and proteolysis in circulation, and PA monomers are internalized via endocytosis. However, endocytotic sequestration and steric hindrance from the lipid tail are two major mechanisms that limit PA efficacy to target intracellular PPIs. To address these problems, we have constructed a PA platform consisting of cathepsin-B cleavable PAs in which a selective p53-based inhibitory peptide is cleaved from its lipid tail within endosomes, allowing for intracellular peptide accumulation and extracellular recycling of the lipid moiety. We monitor for cleavage and follow individual PA components in real time using a resonance energy transfer (FRET)-based tracking system. Using this platform, components in real time using a Forster we provide a better understanding and quantification of cellular internalization, trafficking, and endosomal cleavage of PAs and of the ultimate fates of each component.

  11. Tailoring peptide amphiphiles and their assemblies for biomedical applications

    Science.gov (United States)

    Lin, Brian

    Peptide amphiphiles (PAs) are molecules composed of a peptide conjugated to a hydrophobic moiety, commonly a fatty acid. They closely resemble the structure of naturally occurring lipopeptides, produced by microbes as signaling and antimicrobial agents. The amphiphilic nature of PAs in concert with the large number of discovered functional peptides inspired scientists to exploit this molecular architecture for producing synthetic self-assembled bioactive materials. PA assemblies are sought after for a wide breadth of applications including disease therapy, regenerative medicine, and catalysis. However, with PAs, the peptide chemistry is a double-edged sword. The peptide component contributes significantly to both the activity and self-assembly. The physiochemical properties of different PAs lead to unique aggregation stability and morphological characteristics which are unpredictable, a priori. Therefore it is challenging to design bioactive PAs and control their self-assembly, simultaneously. This limitation slows the development of PAs for medical use. In this dissertation, methods to control the self-assembly of PAs and the effects of acylating a functional peptide will be discussed. In one part, efforts to direct the self-assembly of PAs into small spherical aggregates, a morphology infrequently observed, will be described. In another section, a strategy to control the stability of PA assemblies will be discussed. In the last section, a pH-responsive membrane perturbing peptide was modified with fatty acid tails and the properties of the resulting PAs will be presented. This dissertation provides some fundamental insight for the use and design of PA self-assemblies.

  12. A bioengineered peripheral nerve construct using aligned peptide amphiphile nanofibers

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    Yalom, Anisa; Berns, Eric J.; Stephanopoulos, Nicholas; McClendon, Mark T.; Segovia, Luis A.; Spigelman, Igor; Stupp, Samuel I.; Jarrahy, Reza

    2014-01-01

    Peripheral nerve injuries can result in lifelong disability. Primary coaptation is the treatment of choice when the gap between transected nerve ends is short. Long nerve gaps seen in more complex injuries often require autologous nerve grafts or nerve conduits implemented into the repair. Nerve grafts, however, cause morbidity and functional loss at donor sites, which are limited in number. Nerve conduits, in turn, lack an internal scaffold to support and guide axonal regeneration, resulting in decreased efficacy over longer nerve gap lengths. By comparison, peptide amphiphiles (PAs) are molecules that can self-assemble into nanofibers, which can be aligned to mimic the native architecture of peripheral nerve. As such, they represent a potential substrate for use in a bioengineered nerve graft substitute. To examine this, we cultured Schwann cells with bioactive PAs (RGDS-PA, IKVAV-PA) to determine their ability to attach to and proliferate within the biomaterial. Next, we devised a PA construct for use in a peripheral nerve critical sized defect model. Rat sciatic nerve defects were created and reconstructed with autologous nerve, PLGA conduits filled with various forms of aligned PAs, or left unrepaired. Motor and sensory recovery were determined and compared among groups. Our results demonstrate that Schwann cells are able to adhere to and proliferate in aligned PA gels, with greater efficacy in bioactive PAs compared to the backbone-PA alone. In vivo testing revealed recovery of motor and sensory function in animals treated with conduit/PA constructs comparable to animals treated with autologous nerve grafts. Functional recovery in conduit/PA and autologous graft groups was significantly faster than in animals treated with empty PLGA conduits. Histological examinations also demonstrated increased axonal and Schwann cell regeneration within the reconstructed nerve gap in animals treated with conduit/PA constructs. These results indicate that PA nanofibers may

  13. Composition and method for self-assembly and mineralization of peptide amphiphiles

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    Stupp, Samuel I [Chicago, IL; Beniash, Elia [Newton, MA; Hartgerink, Jeffrey D [Houston, TX

    2009-06-30

    The present invention is directed to a composition useful for making homogeneously mineralized self assembled peptide-amphiphile nanofibers and nanofiber gels. The composition is generally a solution comprised of a positively or negatively charged peptide-amphiphile and a like signed ion from the mineral. Mixing this solution with a second solution containing a dissolved counter-ion of the mineral and/or a second oppositely charged peptide amphiphile, results in the rapid self assembly of the peptide-amphiphiles into a nanofiber gel and templated mineralization of the ions. Templated mineralization of the initially dissolved mineral cations and anions in the mixture occurs with preferential orientation of the mineral crystals along the fiber surfaces within the nanofiber gel. One advantage of the present invention is that it results in homogenous growth of the mineral throughout the nanofiber gel. Another advantage of the present invention is that the nanofiber gel formation and mineralization reactions occur in a single mixing step and under substantially neutral or physiological pH conditions. These homogeneous nanostructured composite materials are useful for medical applications especially the regeneration of damaged bone in mammals. This invention is directed to the synthesis of peptide-amphiphiles with more than one amphiphilic moment and to supramolecular compositions comprised of such multi-dimensional peptide-amphiphiles. Supramolecular compositions can be formed by self assembly of multi-dimensional peptide-amphiphiles by mixing them with a solution comprising a monovalent cation.

  14. Composition and method for self-assembly and mineralization of peptide-amphiphiles

    Science.gov (United States)

    Stupp, Samuel I [Chicago, IL; Beniash, Elia [Newton, MA; Hartgerink, Jeffrey D [Pearland, TX

    2012-02-28

    The present invention is directed to a composition useful for making homogeneously mineralized self assembled peptide-amphiphile nanofibers and nanofiber gels. The composition is generally a solution comprised of a positively or negatively charged peptide-amphiphile and a like signed ion from the mineral. Mixing this solution with a second solution containing a dissolved counter-ion of the mineral and/or a second oppositely charged peptide amphiphile, results in the rapid self assembly of the peptide-amphiphiles into a nanofiber gel and templated mineralization of the ions. Templated mineralization of the initially dissolved mineral cations and anions in the mixture occurs with preferential orientation of the mineral crystals along the fiber surfaces within the nanofiber gel. One advantage of the present invention is that it results in homogenous growth of the mineral throughout the nanofiber gel. Another advantage of the present invention is that the nanofiber gel formation and mineralization reactions occur in a single mixing step and under substantially neutral or physiological pH conditions. These homogeneous nanostructured composite materials are useful for medical applications especially the regeneration of damaged bone in mammals. This invention is directed to the synthesis of peptide-amphiphiles with more than one amphiphilic moment and to supramolecular compositions comprised of such multi-dimensional peptide-amphiphiles. Supramolecular compositions can be formed by self assembly of multi-dimensional peptide-amphiphiles by mixing them with a solution comprising a monovalent cation.

  15. The non-peptidic part determines the internalization mechanism and intracellular trafficking of peptide amphiphiles.

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    Missirlis, Dimitris; Teesalu, Tambet; Black, Matthew; Tirrell, Matthew

    2013-01-01

    Peptide amphiphiles (PAs) are a class of amphiphilic molecules able to self-assemble into nanomaterials that have shown efficient in vivo targeted delivery. Understanding the interactions of PAs with cells and the mechanisms of their internalization and intracellular trafficking is critical in their further development for therapeutic delivery applications. PAs of a novel, cell- and tissue-penetrating peptide were synthesized possessing two different lipophilic tail architectures and their interactions with prostate cancer cells were studied in vitro. Cell uptake of peptides was greatly enhanced post-modification. Internalization occurred via lipid-raft mediated endocytosis and was common for the two analogs studied. On the contrary, we identified the non-peptidic part as the determining factor of differences between intracellular trafficking and retention of PAs. PAs composed of di-stearyl lipid tails linked through poly(ethylene glycol) to the peptide exhibited higher exocytosis rates and employed different recycling pathways compared to ones consisting of di-palmitic-coupled peptides. As a result, cell association of the former PAs decreased with time. Control over peptide intracellular localization and retention is possible by appropriate modification with synthetic hydrophobic tails. We propose this as a strategy to design improved peptide-based delivery systems.

  16. The non-peptidic part determines the internalization mechanism and intracellular trafficking of peptide amphiphiles.

    Directory of Open Access Journals (Sweden)

    Dimitris Missirlis

    Full Text Available BACKGROUND: Peptide amphiphiles (PAs are a class of amphiphilic molecules able to self-assemble into nanomaterials that have shown efficient in vivo targeted delivery. Understanding the interactions of PAs with cells and the mechanisms of their internalization and intracellular trafficking is critical in their further development for therapeutic delivery applications. METHODOLOGY/PRINCIPAL FINDINGS: PAs of a novel, cell- and tissue-penetrating peptide were synthesized possessing two different lipophilic tail architectures and their interactions with prostate cancer cells were studied in vitro. Cell uptake of peptides was greatly enhanced post-modification. Internalization occurred via lipid-raft mediated endocytosis and was common for the two analogs studied. On the contrary, we identified the non-peptidic part as the determining factor of differences between intracellular trafficking and retention of PAs. PAs composed of di-stearyl lipid tails linked through poly(ethylene glycol to the peptide exhibited higher exocytosis rates and employed different recycling pathways compared to ones consisting of di-palmitic-coupled peptides. As a result, cell association of the former PAs decreased with time. CONCLUSIONS/SIGNIFICANCE: Control over peptide intracellular localization and retention is possible by appropriate modification with synthetic hydrophobic tails. We propose this as a strategy to design improved peptide-based delivery systems.

  17. Self-assembling peptide amphiphiles and related methods for growth factor delivery

    Science.gov (United States)

    Stupp, Samuel I [Chicago, IL; Donners, Jack J. J. M.; Silva, Gabriel A [Chicago, IL; Behanna, Heather A [Chicago, IL; Anthony, Shawn G [New Stanton, PA

    2009-06-09

    Amphiphilic peptide compounds comprising one or more epitope sequences for binding interaction with one or more corresponding growth factors, micellar assemblies of such compounds and related methods of use.

  18. Synthesis and evaluation of amphiphilic peptides as nanostructures and drug delivery tools

    Science.gov (United States)

    Sayeh, Naser Ali

    conjugates although one limitation lies in the effort of controlling the rate of drug release. The encapsulated or complexed drugs tend to be released rapidly (before reaching the target site) and in the dendrimer--drug conjugates, it is the chemical linkage that controls the drug release. Thus, future studies in this field are urgently required to create more efficient and stable biomaterials. Peptides are considered as efficient vectors for achieving optimal cellular uptake. The potential use of peptides as drug delivery vectors received much attention by the discovery of several cell-penetrating peptides (CPPs). The first CPPs discovered in 1988, that were sequences from HIV-1 encoded TAT protein, TAT (48--60), and penetrated very efficiently through cell membranes of cultured mammalian cells. CPPs are a class of diverse peptides, typically with 8--25 amino acids, and unlike most peptides, they can cross the cellular membrane with more efficiency. CPPs have also shown to undergo self-assembly and generate nanostructures. The generation of self-assembled peptides and nanostructures occur through various types of interactions between functional groups of amino acid residues, such as electrostatic, hydrophobic, and hydrogen bonding. Appropriate design and functionalization of peptides are critical for generating nanostructures. Chemically CPPs are classified into two major groups: linear and cyclic peptides. It has been previously reported that linear peptides containing hydrophilic and hydrophobic amino acids could act as membrane protein stabilizers. These compounds are short hydrophilic or amphiphilic peptides that have positively charged amino acids, such as arginine, lysine or histidine, which can interact with the negative charge phospholipids layer on the cell membrane and translocate the cargo into the cells. Conjugation to cationic linear CPPs, such as TAT, penetratin, or oligoarginine efficiently improves the cellular uptake of large hydrophilic molecules, but the

  19. An approach to the construction of tailor-made amphiphilic peptides that strongly and selectively bind to hairpin RNA targets.

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    Lee, Su Jin; Hyun, Soonsil; Kieft, Jeffrey S; Yu, Jaehoon

    2009-02-18

    The hairpin RNA motif is one of the most frequently observed secondary structures and is often targeted by therapeutic agents. An amphiphilic peptide with seven lysine and eight leucine residues and its derivatives were designed for use as ligands against RNA hairpin motifs. We hypothesized that variations in both the hydrophobic leucine-rich and hydrophilic lysine-rich spheres of these amphiphilic peptides would create extra attractive interactions with hairpin RNA targets. A series of alanine-scanned peptides were probed to identify the most influential lysine residues in the hydrophilic sphere. The binding affinities of these modified peptides with several hairpins, such as RRE, TAR from HIV, a short hairpin from IRES of HCV, and a hairpin from the 16S A-site stem from rRNA, were determined. Since the hairpin from IRES of HCV was the most susceptible to the initial series of alanine-scanned peptides, studies investigating how further variations in the peptides effect binding employed the IRES hairpin. Next, the important Lys residues were substituted by shorter chain amines, such as ornithine, to place the peptide deeper into the hairpin groove. In a few cases, a 70-fold improved binding was observed for peptides that contained the specifically located shorter amine side chains. To further explore changes in binding affinities brought about by alterations in the hydrophobic sphere, tryptophan residues were introduced in place of leucine. A few peptides with tryptophan in specific positions also displayed 70-fold improved binding affinities. Finally, double mutant peptides incorporating both specifically located shorter amine side chains in the hydrophilic region and tryptophan residues in the hydrophobic region were synthesized. The binding affinities of peptides containing the simple double modification were observed to be 80 times lower, and their binding specificities were increased 40-fold. The results of this effort provide important information about

  20. Tipping the Scale from Disorder to Alpha-helix: Folding of Amphiphilic Peptides in the Presence of Macroscopic and Molecular Interfaces.

    Directory of Open Access Journals (Sweden)

    Cahit Dalgicdir

    2015-08-01

    Full Text Available Secondary amphiphilicity is inherent to the secondary structural elements of proteins. By forming energetically favorable contacts with each other these amphiphilic building blocks give rise to the formation of a tertiary structure. Small proteins and peptides, on the other hand, are usually too short to form multiple structural elements and cannot stabilize them internally. Therefore, these molecules are often found to be structurally ambiguous up to the point of a large degree of intrinsic disorder in solution. Consequently, their conformational preference is particularly susceptible to environmental conditions such as pH, salts, or presence of interfaces. In this study we use molecular dynamics simulations to analyze the conformational behavior of two synthetic peptides, LKKLLKLLKKLLKL (LK and EAALAEALAEALAE (EALA, with built-in secondary amphiphilicity upon forming an alpha-helix. We use these model peptides to systematically study their aggregation and the influence of macroscopic and molecular interfaces on their conformational preferences. We show that the peptides are neither random coils in bulk water nor fully formed alpha helices, but adopt multiple conformations and secondary structure elements with short lifetimes. These provide a basis for conformation-selection and population-shift upon environmental changes. Differences in these peptides' response to macroscopic and molecular interfaces (presented by an aggregation partner can be linked to their inherent alpha-helical tendencies in bulk water. We find that the peptides' aggregation behavior is also strongly affected by presence or absence of an interface, and rather subtly depends on their surface charge and hydrophobicity.

  1. Intrinsically disordered amphiphilic peptides as potential targets in drug delivery vehicles.

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    Vincenzi, Marian; Accardo, Antonella; Costantini, Susan; Scala, Stefania; Portella, Luigi; Trotta, Annamaria; Ronga, Luisa; Guillon, Jean; Leone, Marilisa; Colonna, Giovanni; Rossi, Filomena; Tesauro, Diego

    2015-11-01

    Intrinsically disordered proteins/peptides play a crucial role in many physiological and pathological events and may assume a precise conformation upon binding to a specific target. Recently, we have described the conformational and functional properties of two linear ester peptides provided with the following sequences: Y-G-E-C-P-C-K-OAllyl (PepK) and Y-G-E-C-P-C-E-OAllyl (PepE). Both peptides are characterized by the presence of the "CPC" motif together with a few amino acids able to promote disorder. The CPC sequence is a binding motif for the CXCR4 receptor that represents a well-known target for cancer therapies. In this paper, we report on synthetic amphiphilic peptides that consist of lipophilic derivatives of PepE and PepK bearing two stearic alkyl chains and/or an ethoxylic spacer. These peptide amphiphiles form stable supramolecular aggregates; they present conformational features that are typical of intrinsically disordered molecules as shown by CD spectroscopy. Solution fluorescence and DLS studies have been performed to evaluate Critical Micellar Concentrations and the dimension of supramolecular aggregates. Moreover, preliminary in vitro cell-based assays have been conducted to investigate the molecular recognition processes involving the CXCR4 receptor. In the end, the results obtained have been compared with the previous data generated by the corresponding non-amphiphilic peptides (PepE and PepK).

  2. Nanostructures by self-assembling peptide amphiphile as potential selective drug carriers.

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    Accardo, Antonella; Tesauro, Diego; Mangiapia, Gaetano; Pedone, Carlo; Morelli, Giancarlo

    2007-01-01

    The self-assembling behavior, at physiological pH, of the amphiphile peptide (C18)(2)L5CCK8 in nanostructures is reported. Stable aggregates presenting a critical micellar concentration of 2 x 10(-6) mol kg(-1), and characterized by water exposed CCK8 peptide in beta-sheet conformation, are obtained. Small angle neutron scattering experiments are indicative for a 3D structure with dimensions > or =100 nm. AFM images confirm the presence of nanostructures. Fluorescence experiments indicating the sequestration of pyrene, chosen as drug model, and the anticancer Doxorubicin within the nanostructures are reported.

  3. Internalization of p53(14-29) peptide amphiphiles and subsequent endosomal disruption results in SJSA-1 cell death.

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    Missirlis, Dimitris; Krogstad, Daniel V; Tirrell, Matthew

    2010-12-06

    In vivo peptide inhibition of tumor suppressor p53 binding to the protein MDM2 is hampered by inefficient delivery of the peptide. Our approach to couple a hydrophobic lipid-like tail on the inhibitory peptide p53(14-29) allowed its intracellular delivery in vitro, in a panel of different cell lines. The constructed chimeric molecules, termed peptide amphiphiles, further self-assembled into supramolecular structures, identified as elongated wormlike micelles. Internalization of peptides occurred following micelle disassembly, partly via clathrin-mediated endocytosis of monomers. Incubation of SJSA-1 cells in hypertonic culture media, aimed to disrupt endocytic vesicles, resulted in peptide amphiphile-mediated cell death. Our results provide the basis for the construction of novel therapeutic supramolecular nanoparticles and suggest hydrophobic modification of peptides as a promising strategy for enhancing delivery of impermeable peptides.

  4. Design and synthesis of short amphiphilic cationic peptidomimetics based on biphenyl backbone as antibacterial agents.

    Science.gov (United States)

    Kuppusamy, Rajesh; Yasir, Muhammad; Berry, Thomas; Cranfield, Charles G; Nizalapur, Shashidhar; Yee, Eugene; Kimyon, Onder; Taunk, Aditi; Ho, Kitty K K; Cornell, Bruce; Manefield, Mike; Willcox, Mark; Black, David StC; Kumar, Naresh

    2018-01-01

    Antimicrobial peptides (AMPs) and their synthetic mimics have received recent interest as new alternatives to traditional antibiotics in attempts to overcome the rise of antibiotic resistance in many microbes. AMPs are part of the natural defenses of most living organisms and they also have a unique mechanism of action against bacteria. Herein, a new series of short amphiphilic cationic peptidomimetics were synthesized by incorporating the 3'-amino-[1,1'-biphenyl]-3-carboxylic acid backbone to mimic the essential properties of natural AMPs. By altering hydrophobicity and charge, we identified the most potent analogue 25g that was active against both Gram-positive Staphylococcus aureus (MIC = 15.6 μM) and Gram-negative Escherichia coli (MIC = 7.8 μM) bacteria. Cytoplasmic permeability assay results revealed that 25g acts primarily by depolarization of lipids in cytoplasmic membranes. The active compounds were also investigated for their cytotoxicity to human cells, lysis of lipid bilayers using tethered bilayer lipid membranes (tBLMs) and their activity against established biofilms of S. aureus and E. coli. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  5. A molecular model for membrane fusion based on solution studies of an amphiphilic peptide from HIV gp41.

    OpenAIRE

    Fujii, G.; Horvath, S.; Woodward, S.; Eiserling, F.; Eisenberg, D.

    1992-01-01

    The mechanism of protein-mediated membrane fusion and lysis has been investigated by solution-state studies of the effects of peptides on liposomes. A peptide (SI) corresponding to a highly amphiphilic C-terminal segment from the envelope protein (gp41) of the human immunodeficiency virus (HIV) was synthesized and tested for its ability to cause lipid membranes to fuse together (fusion) or to break open (lysis). These effects were compared to those produced by the lytic and fusogenic peptide ...

  6. The Osteogenic Differentiation Effect of the FN Type 10-Peptide Amphiphile on PCL Fiber

    Directory of Open Access Journals (Sweden)

    Ye-Rang Yun

    2018-01-01

    Full Text Available The fibronectin type 10-peptide amphiphile (FNIII10-PA was previously genetically engineered and showed osteogenic differentiation activity on rat bone marrow stem cells (rBMSCs. In this study, we investigated whether FNIII10-PA demonstrated cellular activity on polycaprolactone (PCL fibers. FNIII10-PA significantly increased protein production and cell adhesion activity on PCL fibers in a dose-dependent manner. In cell proliferation results, there was no effect on cell proliferation activity by FNIII10-PA; however, FNIII10-PA induced the osteogenic differentiation of MC3T3-E1 cells via upregulation of bone sialoprotein (BSP, collagen type I (Col I, osteocalcin (OC, osteopontin (OPN, and runt-related transcription factor 2 (Runx2 mitochondrial RNA (mRNA levels; it did not increase the alkaline phosphatase (ALP mRNA level. These results indicate that FNIII10-PA has potential as a new biomaterial for bone tissue engineering applications.

  7. Shear Alignment of Bola-Amphiphilic Arginine-Coated Peptide Nanotubes.

    Science.gov (United States)

    Hamley, Ian W; Burholt, Samuel; Hutchinson, Jessica; Castelletto, Valeria; da Silva, Emerson Rodrigo; Alves, Wendel; Gutfreund, Philipp; Porcar, Lionel; Dattani, Rajeev; Hermida-Merino, Daniel; Newby, Gemma; Reza, Mehedi; Ruokolainen, Janne; Stasiak, Joanna

    2017-01-09

    The bola-amphiphilic arginine-capped peptide RFL 4 RF self-assembles into nanotubes in aqueous solution. The nanostructure and rheology are probed by in situ simultaneous rheology/small-angle scattering experiments including rheo-SAXS, rheo-SANS, and rheo-GISANS (SAXS: small-angle X-ray scattering, SANS: small-angle neutron scattering, GISANS: grazing incidence small-angle neutron scattering). Nematic alignment of peptide nanotubes under shear is observed at sufficiently high shear rates under steady shear in either Couette or cone-and-plate geometry. The extent of alignment increases with shear rate. A shear plateau is observed in a flow curve measured in the Couette geometry, indicating the presence of shear banding above the shear rate at which significant orientation is observed (0.1-1 s -1 ). The orientation under shear is transient and is lost as soon as shear is stopped. GISANS shows that alignment at the surface of a cone-and-plate cell develops at sufficiently high shear rates, very similar to that observed in the bulk using the Couette geometry. A small isotope effect (comparing H 2 O/D 2 O solvents) is noted in the CD spectra indicating increased interpeptide hydrogen bonding in D 2 O, although this does not influence nanotube self-assembly. These results provide new insights into the controlled alignment of peptide nanotubes for future applications.

  8. Synthesis and bioactivities study of new antibacterial peptide mimics: The dialkyl cationic amphiphiles.

    Science.gov (United States)

    Zhang, En; Bai, Peng-Yan; Cui, De-Yun; Chu, Wen-Chao; Hua, Yong-Gang; Liu, Qin; Yin, Hai-Yang; Zhang, Yong-Jie; Qin, Shangshang; Liu, Hong-Min

    2018-01-01

    The emergence of infectious diseases caused by pathogenic bacteria is widespread. Therefore, it is urgently required to enhance the development of novel antimicrobial agents with high antibacterial activity and low cytotoxicity. A series of novel dialkyl cationic amphiphiles bearing two identical length lipophilic alkyl chains and one non-peptidic amide bond were synthesized and tested for antimicrobial activities against both Gram-positive and Gram-negative bacteria. Particular compounds synthesized showed excellent antibacterial activity toward drug-sensitive bacteria such as S. aureus, E. faecalis, E. coli and S. enterica, and clinical isolates of drug-resistant species such as methicillin-resistant S. aureus (MRSA), KPC-producing and NDM-1-producing carbapenem-resistant Enterobacteriaceae (CRE). For example, the MIC values of the best compound 4g ranged from 0.5 to 2 μg/mL against all these strains. Moreover, these small molecules acted rapidly as bactericidal agents, and functioned primarily by permeabilization and depolarization of bacterial membranes. Importantly, these compounds were difficult to induce bacterial resistance and can potentially combat drug-resistant bacteria. Thus, these compounds can be developed into a new class of antibacterial peptide mimics against Gram-positive and Gram-negative bacteria, including drug-resistant bacterial strains. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  9. Control over Structure and Function of Peptide Amphiphile Supramolecular Assemblies through Molecular Design and Energy Landscapes

    Science.gov (United States)

    Tantakitti, Faifan

    Supramolecular chemistry is a powerful tool to create a material of a defined structure with tunable properties. This strategy has led to catalytically active, bioactive, and environment-responsive materials, among others, that are valuable in applications ranging from sensor technology to energy and medicine. Supramolecular polymers formed by peptide amphiphiles (PAs) have been especially relevant in tissue regeneration due to their ability to form biocompatible structures and mimic many important signaling molecules in biology. These supramolecular polymers can form nanofibers that create networks which mimic natural extracellular matrices. PA materials have been shown to induce growth of blood vessels, bone, cartilage, and nervous tissue, among others. The work described in this thesis not only studied the relationship between molecular structure and functions of PA assemblies, but also uncovered a powerful link between the energy landscape of their supramolecular self-assembly and the ability of PA materials to interact with cells. In chapter 2, it is argued that fabricating fibrous nanostructures with defined mechanical properties and decoration with bioactive molecules is not sufficient to create a material that can effectively communicate with cells. By systemically placing the fibronectin-derived RGDS epitope at increasing distances from the surface of PA nanofibers through a linker of one to five glycine residues, integrin-mediated RGDS signaling was enhanced. The results suggested that the spatial presentation of an epitope on PA nanofibers strongly influences the bioactivity of the PA substrates. In further improving functionality of a PA-based scaffold to effectively direct cell growth and differentiation, chapter 3 explored the use of a cell microcarrier to compartmentalize and simultaneously tune insoluble and soluble signals in a single matrix. PA nanofibers were incorporated at the surface of the microcarrier in order to promote cell adhesion, while

  10. A molecular model for membrane fusion based on solution studies of an amphiphilic peptide from HIV gp41.

    Science.gov (United States)

    Fujii, G; Horvath, S; Woodward, S; Eiserling, F; Eisenberg, D

    1992-11-01

    The mechanism of protein-mediated membrane fusion and lysis has been investigated by solution-state studies of the effects of peptides on liposomes. A peptide (SI) corresponding to a highly amphiphilic C-terminal segment from the envelope protein (gp41) of the human immunodeficiency virus (HIV) was synthesized and tested for its ability to cause lipid membranes to fuse together (fusion) or to break open (lysis). These effects were compared to those produced by the lytic and fusogenic peptide from bee venom, melittin. Other properties studied included the changes in visible absorbance and mean particle size, and the secondary structure of peptides as judged by CD spectroscopy. Taken together, the observations suggest that protein-mediated membrane fusion is dependent not only on hydrophobic and electrostatic forces but also on the spatial arrangement of the amino acid residues to form an amphiphilic structure that promotes the mixing of the lipids between membranes. A speculative molecular model is proposed for membrane fusion by alpha-helical peptides, and its relationship to the forces involved in protein-membrane interactions is discussed.

  11. Co-assembly of Peptide Amphiphiles and Lipids into Supramolecular Nanostructures Driven by Anion-π Interactions

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Zhilin; Erbas, Aykut; Tantakitti, Faifan; Palmer, Liam C.; Jackman, Joshua A.; Olvera de la Cruz, Monica; Cho, Nam-Joon; Stupp, Samuel I. (Nanyang); (NWU)

    2017-06-01

    Co-assembly of binary systems driven by specific non-covalent interactions can greatly expand the structural and functional space of supramolecular nanostructures. We report here on the self-assembly of peptide amphiphiles and fatty acids driven primarily by anion-π interactions. The peptide sequences investigated were functionalized with a perfluorinated phenylalanine residue to promote anion-π interactions with carboxylate headgroups in fatty acids. These interactions were verified here by NMR and circular dichroism experiments as well as investigated using atomistic simulations. Positioning the aromatic units close to the N-terminus of the peptide backbone near the hydrophobic core of cylindrical nanofibers leads to strong anion-π interactions between both components. With a low content of dodecanoic acid in this position, the cylindrical morphology is preserved. However, as the aromatic units are moved along the peptide backbone away from the hydrophobic core, the interactions with dodecanoic acid transform the cylindrical supramolecular morphology into ribbon-like structures. Increasing the ratio of dodecanoic acid to PA leads to either the formation of large vesicles in the binary systems where the anion-π interactions are strong, or a heterogeneous mixture of assemblies when the peptide amphiphiles associate weakly with dodecanoic acid. Our findings reveal how co-assembly involving designed specific interactions can drastically change supramolecular morphology and even cross from nano to micro scales.

  12. Bio-fabrication and physiological self-release of tissue equivalents using smart peptide amphiphile templates.

    Science.gov (United States)

    Gouveia, Ricardo M; Hamley, Ian W; Connon, Che J

    2015-10-01

    In this study we applied a smart biomaterial formed from a self-assembling, multi-functional synthetic peptide amphiphile (PA) to coat substrates with various surface chemistries. The combination of PA coating and alignment-inducing functionalised substrates provided a template to instruct human corneal stromal fibroblasts to adhere, become aligned and then bio-fabricate a highly-ordered, multi-layered, three-dimensional tissue by depositing an aligned, native-like extracellular matrix. The newly-formed corneal tissue equivalent was subsequently able to eliminate the adhesive properties of the template and govern its own complete release via the action of endogenous proteases. Tissues recovered through this method were structurally stable, easily handled, and carrier-free. Furthermore, topographical and mechanical analysis by atomic force microscopy showed that tissue equivalents formed on the alignment-inducing PA template had highly-ordered, compact collagen deposition, with a two-fold higher elastic modulus compared to the less compact tissues produced on the non-alignment template, the PA-coated glass. We suggest that this technology represents a new paradigm in tissue engineering and regenerative medicine, whereby all processes for the bio-fabrication and subsequent self-release of natural, bio-prosthetic human tissues depend solely on simple template-tissue feedback interactions.

  13. Biphasic Peptide Amphiphile Nanomatrix Embedded with Hydroxyapatite Nanoparticles for Stimulated Osteoinductive Response

    Science.gov (United States)

    Anderson, Joel M.; Patterson, Jessica L.; Vines, Jeremy B.; Javed, Amjad; Gilbert, Shawn R.; Jun, Ho-Wook

    2013-01-01

    Formation of the native bone extracellular matrix (ECM) provides an attractive template for bone tissue engineering. The structural support and biological complexity of bone ECM are provided within a composite microenvironment that consists of an organic fibrous network reinforced by inorganic hydroxyapatite (HA) nanoparticles. Recreating this biphasic assembly, a bone ECM analogous scaffold comprised of self-assembling peptide amphiphile (PA) nanofibers and interspersed HA nanoparticles was investigated. PAs were endowed with biomolecular ligand signaling using a synthetically inscribed peptide sequence (i.e. RGDS) and integrated with HA nanoparticles to form a biphasic nanomatrix hydrogel. It was hypothesized the biphasic hydrogel would induce osteogenic differentiation of human mesenchymal stem cells (hMSCs) and improve bone healing as mediated by RGDS ligand signaling within PA nanofibers and embedded HA mineralization source. Viscoelastic stability of the biphasic PA hydrogels was evaluated with different weight concentrations of HA for improved gelation. After demonstrating initial viability, long-term cellularity and osteoinduction of encapsulated hMSCs in different PA hydrogels were studied in vitro. Temporal progression of osteogenic maturation was assessed by gene expression of key markers. A preliminary animal study demonstrated bone healing capacity of the biphasic PA nanomatrix under physiological conditions using a critical size femoral defect rat model. The combination of RGDS ligand signaling and HA nanoparticles within the biphasic PA nanomatrix hydrogel demonstrated the most effective osteoinduction and comparative bone healing response. Therefore, the biphasic PA nanomatrix establishes a well-organized scaffold with increased similarity to natural bone ECM with the prospect for improved bone tissue regeneration. PMID:22077993

  14. Covalent Functionalization of NiTi Surfaces with Bioactive Peptide Amphiphile Nanofibers

    Science.gov (United States)

    Sargeant, Timothy D.; Rao, Mukti S.; Koh, Chung-Yan

    2009-01-01

    Surface modification enables the creation of bioactive implants using traditional material substrates without altering the mechanical properties of the bulk material. For applications such as bone plates and stents, it is desirable to modify the surface of metal alloy substrates to facilitate cellular attachment, proliferation, and possibly differentiation. In this work we present a general strategy for altering the surface chemistry of nickel-titanium shape memory alloy (NiTi) in order to covalently attach self-assembled peptide amphiphile (PA) nanofibers with bioactive functions. Bioactivity in the systems studied here includes biological adhesion and proliferation of osteoblast and endothelial cell types. The optimized surface treatment creates a uniform TiO2 layer with low levels of Ni on the NiTi surface, which is subsequently covered with an aminopropylsilane coating using a novel, lower temperature vapor deposition method. This method produces an aminated surface suitable for covalent attachment of PA molecules containing terminal carboxylic acid groups. The functionalized NiTi surfaces have been characterized by X-ray photoelectron spectroscopy (XPS), time-of-flight secondary ion mass spectroscopy (ToF-SIMS), and atomic force microscopy (AFM). These techniques offer evidence that the treated metal surfaces consist primarily of TiO2 with very little Ni, and also confirm the presence of the aminopropylsilane overlayer. Self-assembled PA nanofibers presenting the biological peptide adhesion sequence Arg-Gly-Asp-Ser are capable of covalently anchoring to the treated substrate, as demonstrated by spectrofluorimetry and AFM. Cell culture and scanning electron microscopy (SEM) demonstrate cellular adhesion, spreading, and proliferation on these functionalized metal surfaces. Furthermore, these experiments demonstrate that covalent attachment is crucial for creating robust PA nanofiber coatings, leading to confluent cell monolayers. PMID:18083225

  15. Synthetic β-sheet forming peptide amphiphiles for treatment of fungal keratitis.

    Science.gov (United States)

    Wu, Hong; Ong, Zhan Yuin; Liu, Shaoqiong; Li, Yan; Wiradharma, Nikken; Yang, Yi Yan; Ying, Jackie Y

    2015-03-01

    Fungal keratitis is a leading cause of ocular morbidity. It is frequently misdiagnosed as bacterial keratitis, causing a delay in proper treatment. Furthermore, due to the lack of safe and effective anti-fungal agents for clinical use, treatment of fugal keratitis remains a challenge. In recent years, antimicrobial peptides (AMPs) have received considerable attention as potent and broad-spectrum antimicrobial agents with the potential to overcome antibiotics resistance. We previously reported the design of short synthetic β-sheet forming peptides (IKIK)2-NH2 and (IRIK)2-NH2 with excellent antimicrobial activities and selectivities against various clinically relevant microorganisms, including Gram-positive Staphylococcus epidermidis and Staphylococcus aureus, Gram-negative Escherichia coli and Pseudomonas aeruginosa, and yeast Candida albicans (C. albicans). In this study, we evaluated the application of the two most promising synthetic β-sheet forming peptide candidates for in vivo fungal keratitis treatment in comparison with the commercially available amphotericin B. It was found that topical solutions of the designed peptides are safe, and as effective as the clinically used amphotericin B. Compared to the costly and unstable amphotericin B, (IKIK)2-NH2 and (IRIK)2-NH2 are water-soluble, less expensive and stable. Thus, the synthetic β-sheet forming peptides are presented as promising candidates for the treatment of fungal keratitis. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Creating a stem cell niche in the inner ear using self-assembling peptide amphiphiles

    Science.gov (United States)

    Sayed, Zafar A.; Stephanopoulos, Nicholas; Berns, Eric J.; Wadhwani, Anil R.; Morrissey, Zachery D.; Chadly, Duncan M.; Kobayashi, Shun; Edelbrock, Alexandra N.; Mashimo, Tomoji; Miller, Charles A.; McGuire, Tammy L.; Stupp, Samuel I.; Kessler, John A.

    2017-01-01

    The use of human embryonic stem cells (hESCs) for regeneration of the spiral ganglion will require techniques for promoting otic neuronal progenitor (ONP) differentiation, anchoring of cells to anatomically appropriate and specific niches, and long-term cell survival after transplantation. In this study, we used self-assembling peptide amphiphile (PA) molecules that display an IKVAV epitope (IKVAV-PA) to create a niche for hESC-derived ONPs that supported neuronal differentiation and survival both in vitro and in vivo after transplantation into rodent inner ears. A feature of the IKVAV-PA gel is its ability to form organized nanofibers that promote directed neurite growth. Culture of hESC-derived ONPs in IKVAV-PA gels did not alter cell proliferation or viability. However, the presence of IKVAV-PA gels increased the number of cells expressing the neuronal marker beta-III tubulin and improved neurite extension. The self-assembly properties of the IKVAV-PA gel allowed it to be injected as a liquid into the inner ear to create a biophysical niche for transplanted cells after gelation in vivo. Injection of ONPs combined with IKVAV-PA into the modiolus of X-SCID rats increased survival and localization of the cells around the injection site compared to controls. Human cadaveric temporal bone studies demonstrated the technical feasibility of a transmastoid surgical approach for clinical intracochlear injection of the IKVAV-PA/ONP combination. Combining stem cell transplantation with injection of self-assembling PA gels to create a supportive niche may improve clinical approaches to spiral ganglion regeneration. PMID:29284013

  17. Creating a stem cell niche in the inner ear using self-assembling peptide amphiphiles.

    Directory of Open Access Journals (Sweden)

    Akihiro J Matsuoka

    Full Text Available The use of human embryonic stem cells (hESCs for regeneration of the spiral ganglion will require techniques for promoting otic neuronal progenitor (ONP differentiation, anchoring of cells to anatomically appropriate and specific niches, and long-term cell survival after transplantation. In this study, we used self-assembling peptide amphiphile (PA molecules that display an IKVAV epitope (IKVAV-PA to create a niche for hESC-derived ONPs that supported neuronal differentiation and survival both in vitro and in vivo after transplantation into rodent inner ears. A feature of the IKVAV-PA gel is its ability to form organized nanofibers that promote directed neurite growth. Culture of hESC-derived ONPs in IKVAV-PA gels did not alter cell proliferation or viability. However, the presence of IKVAV-PA gels increased the number of cells expressing the neuronal marker beta-III tubulin and improved neurite extension. The self-assembly properties of the IKVAV-PA gel allowed it to be injected as a liquid into the inner ear to create a biophysical niche for transplanted cells after gelation in vivo. Injection of ONPs combined with IKVAV-PA into the modiolus of X-SCID rats increased survival and localization of the cells around the injection site compared to controls. Human cadaveric temporal bone studies demonstrated the technical feasibility of a transmastoid surgical approach for clinical intracochlear injection of the IKVAV-PA/ONP combination. Combining stem cell transplantation with injection of self-assembling PA gels to create a supportive niche may improve clinical approaches to spiral ganglion regeneration.

  18. Salt effects on the sol-gel transitions of aqueous peptide-amphiphile solutions

    Science.gov (United States)

    Yamamoto, Masashi; Maeda, Tomoki; Hotta, Atsushi

    A hydrogel made of a peptide amphiphile (PA) is an interesting soft material especially in the biomedical fields due to its controllable nanoscale structures with excellent biocompatibility. To extend the practical use of PA, a comprehensive study of the sol-gel transitions of PA is necessary to be used as e.g. a biomedical material. The effects of the types of salts in our body or in medicinal agents on the physical properties of the PA solution are not fully understood. In this study, different types of salt with various negative ions were added to a PA (C16-W3K) solution. The salt effects on the rheological properties, the pH, and the zeta potentials of the PA solutions were studied. From the rheological testing, it was found that the C16-W3K solutions could not gelate in the presence of Na2CO3 or Na3PO4, which could be caused by the aggregation of the wormlike micelles made of C16-W3K. pH-wise, the sol-gel transitions could be observed only when the PA solutions were relatively acidic (the Zeta potential was positive) instead of basic (the Zeta potential was very negative) . It was therefore concluded that the sol-gel transitions of the PA solution could be effectively controlled by the types of salt. This work was supported by a Grant-in-Aid for Scientific Research (A) (No. 15H02298 to A.H.) and a Grant-in-Aid for Research Activity Start-up (No.15H06586 to T.M.) from JSPS: KAKENHI.

  19. Hierarchical Self-Assembly of Peptide Amphiphiles: Form and Function at Multiple Length Scales

    Science.gov (United States)

    Zha, Runye Helen

    Hierarchical self-assembly, the organization of molecules into supramolecular structures of increasing size and complexity, is a potent tool for materials synthesis and requires understanding the connections of structure across multiple length scales. Herein, self-assembly of peptide amphiphiles (PAs) into nanoscopic and macroscopic materials is explored, and their anti-cancer applications are investigated. First, nanoscale assembly is examined in the context of an anti-angiogenic PA bearing the G-helix motif of maspin, a tumor suppressor protein. Assembly of this maspin-mimetic PA (MMPA) stabilizes the native G-helix conformation and improves binding to endothelial cells. Furthermore, PA nanostructures significantly increase cell adhesion to fibronectin as compared to G-helix peptide alone. Combined with its inhibitory effect on cell migration, MMPA nanostructures thus show anti-angiogenic activity on par with maspin protein in vitro and in vivo. Second, assembly of cationic PAs with hyaluronic acid (HA), an anionic polyelectrolyte, into macroscopic membranes is explored using PAs with identical formal charge but systematically varied self-assembly domains. Results suggest that membrane formation is dictated by the initial moments of component aggregation and is highly sensitive to PA molecular structure via nanoscale assembly. Specifically, PAs with beta-sheet forming residues are nanofibrous and have high surface charge density, leading to robust membranes with aligned-fiber microstructure. PAs without beta-sheet forming residues are nanospherical and have low surface charge density, leading to weak membranes with non-fibrous finger-like microstructure. Lastly, the principles of PA-HA membrane assembly are applied towards development of anti-cancer therapeutic biomaterials. Here, cytotoxic PAs bearing the epitope (KLAKLAKbeta)2 are co-assembled with non-bioactive cationic PA in order to achieve varying nanoscale morphology. These nanostructures are then

  20. Effects of N-terminal and C-terminal modification on cytotoxicity and cellular uptake of amphiphilic cell penetrating peptides.

    Science.gov (United States)

    Soleymani-Goloujeh, Mehdi; Nokhodchi, Ali; Niazi, Mehri; Najafi-Hajivar, Saeedeh; Shahbazi-Mojarrad, Javid; Zarghami, Nosratollah; Zakeri-Milani, Parvin; Mohammadi, Ali; Karimi, Mohammad; Valizadeh, Hadi

    2017-12-19

    To assess the effect of "N-Acetylation and C-Amidation" on the cellular uptake, cytotoxicity and performance of amphiphilic cell penetrating peptides (CPP) loaded with methotrexate (MTX). Several CPPs were synthesized by solid phase peptide synthesis method. Some of these sequences were modified with pyroglutamic acid at N-terminus and benzylamine or memantine at C-terminus. The resultant nanomaterials were prepared due to the physical linkage between CPPs and MTX. The internalization and cytotoxicity of both CPP-MTX bioconjugates and unmodified CPPs against MCF-7 human breast adenocarcinoma cells was evaluated. N-l and C-terminal modification did not alter the toxicity of CPPs. Physical linkage of CPPs with MTX resulted in a lower drug loading efficiency in comparison with chemically conjugated CPP-MTX bio-conjugates. Both nano-complexes increase the toxic effect of MTX on MCF-7 cells. Furthermore, N- and C-terminal modification may cause a tangible reduction in cellular uptake of CPPs. In conclusion, it was shown that cytotoxicity of modified peptides which were physically linked with MTX, considerably higher than both physically loaded unmodified peptides and chemically conjugated peptides with MTX. Also, cell internalization was reduced after peptide end-protection. These findings confirmed the effectiveness of N- and C-terminal modifications on cell viability and CPPs internalization.

  1. Solution conformational features and interfacial properties of an intrinsically disordered peptide coupled to alkyl chains: a new class of peptide amphiphiles.

    Science.gov (United States)

    Accardo, Antonella; Leone, Marilisa; Tesauro, Diego; Aufiero, Rosa; Bénarouche, Anaïs; Cavalier, Jean-François; Longhi, Sonia; Carriere, Frederic; Rossi, Filomena

    2013-06-01

    Owing to the large panel of biological functions of peptides and their high specificity and potency, the development of peptide-based therapeutic and diagnostic tools has received increasing interest. Peptide amphiphiles (PAs) are an emerging class of molecules in which a bioactive peptide is covalently conjugated to a hydrophobic moiety. Due to the coexistence in the molecule of a hydrophilic peptide sequence and a hydrophobic group, PAs are able to self-assemble spontaneously into a variety of nanostructures, such as monolayers, bilayers, and vesicles. In this work we have synthesized a disordered peptide, henceforth called R11, and two lipophilic derivatives of R11 bearing two alkyl chains, connected or not to R11 by an ethoxylic-based linker. The structural properties in solution of these new PAs were investigated using CD and NMR. R11 lipophilic derivatives display typical features of PAs, such as the formation of micelles and unilamellar vesicles. In addition, their surface properties were studied using Langmuir monomolecular films and the results obtained support the formation of molecular aggregates upon compression of the PA films. The presence of the alkyl chains induces not only the self-assembly of these new PAs into supramolecular aggregates but also a gain of structure within the disordered peptide.

  2. Structures of self-assembled amphiphilic peptide-heterodimers: effects of concentration, pH, temperature and ionic strength

    KAUST Repository

    Luo, Zhongli

    2010-01-01

    The amphiphilic double-tail peptides AXG were studied regarding secondary structure and self-assembly in aqueous solution. The two tails A = Ala 6 and G = Gly6 are connected by a central pair X of hydrophilic residues, X being two aspartic acids in ADG, two lysines in AKG and two arginines in ARG. The peptide AD (Ala6Asp) served as a single-tail reference. The secondary structure of the four peptides was characterized by circular dichroism spectroscopy under a wide range of peptide concentrations (0.01-0.8 mM), temperatures (20-98 °C), pHs (4-9.5) and ionic strengths. In salt-free water both ADG and AD form a β-sheet type of structure at high concentration, low pH and low temperature, in a peptide-peptide driven assembly of individual peptides. The transition has a two-state character for ADG but not for AD, which indicates that the added tail in ADG makes the assembly more cooperative. By comparison the secondary structures of AKG and ARG are comparatively stable over the large range of conditions covered. According to dynamic light scattering the two-tail peptides form supra-molecular aggregates in water, but high-resolution AFM-imaging indicate that ordered (self-assembled) structures are only formed when salt (0.1 M NaCl) is added. Since the CD-studies indicate that the NaCl has only a minor effect on the peptide secondary structure we propose that the main role of the added salt is to screen the electrostatic repulsion between the peptide building blocks. According to the AFM images ADG and AKG support a correlation between nanofibers and a β-sheet or unordered secondary structure, whereas ARG forms fibers in spite of lacking β-sheet structure. Since the AKG and ARG double-tail peptides self-assemble into distinct nanostructures while their secondary structures are resistant to environment factors, these new peptides show potential as robust building blocks for nano-materials in various medical and nanobiotechnical applications. © 2010 The Royal Society

  3. Antimalarial Activity of Ultra-Short Peptides

    Directory of Open Access Journals (Sweden)

    María Yolanda Rios

    2009-12-01

    Full Text Available Ultra-short peptides 1-9 were designed and synthesized with phenylalanine, ornithine and proline amino acid residues and their effect on antimalarial activity was analyzed. On the basis of the IC50 data for these compounds, the effects of nature, polarity, and amino acid sequence on Plasmodium berghei schizont cultures were analyzed too. Tetrapeptides Phe-Orn-Phe-Orn (4 and Lys-Phe-Phe-Orn (5 showed a very important activity with IC50 values of 3.31 and 2.57 μM, respectively. These two tetrapeptides are candidates for subsequent in vivo assays and SARS investigations.

  4. Affinity study on bovine serum albumin's peptides to amphiphilic gold nanoparticles: A test of epitopes and non-epitopes

    Science.gov (United States)

    Yuan, Ming; Li, Wanrong; Yang, Mingming; Huang, Xiufeng; Bai, Zhijun; Liu, Yushuang; Cai, Weijun; Wang, Yuqin; Zhang, Feng

    2017-09-01

    It is an inevitable event that nanoparticles (NPs) will encounter proteins/peptides in nano-medicine, so it has been significant to know their interaction mechanism before in vivo applications. Previously, a 105-amino-acid sequence had been reported as the binding site between bovine serum albumin (BSA) and amphiphilic polymer coated gold nanoparticles (AP-AuNPs) along with a mortise-tenon joint hypothesis. This article tested the affinity difference between two epitope peptide sequences such as: LGEYGFQNALIVR (S1), DAFLGSFLYEYSR (S2) and one non-epitope peptide sequence as: FDEHVKLVNELTEF (S3). With the photoluminescent amino acid residues, the fluorescence quenching method based on the nanometal surface energy transfer (NSET) principle was able to study the thermodynamics of the current binding system. The binding constants (Ka) were determined and followed the order as: Ka-S1 > Ka-S2 >> Ka-S3. Moreover, Hill constants indicated that cooperativity only presented in the interactions of AP-AuNP with either S1 or S2, but not for S3. Moreover, gel electrophoresis, surface plasmon resonance, atomic force microscopy and three dimensional fluorescence microscopy were all also used to comprehensively analyse the binding interaction mechanism. These results further provided useful information to better understand the mortise-tenon joint, which might find applications to nanofabrication and biomedicine.

  5. Self-assembled or mixed peptide amphiphile micelles from Herpes simplex virus glycoproteins as potential immunomodulatory treatment.

    Science.gov (United States)

    Accardo, Antonella; Vitiello, Mariateresa; Tesauro, Diego; Galdiero, Marilena; Finamore, Emiliana; Martora, Francesca; Mansi, Rosalba; Ringhieri, Paola; Morelli, Giancarlo

    2014-01-01

    The use of micelle aggregates formed from peptide amphiphiles (PAs) as potential synthetic self-adjuvant vaccines to treat Herpes simplex virus (HSV) infection are reported here. The PAs were based on epitopes gB409-505 and gD301-309, selected from HSV envelope glycoprotein B (gB) and glycoprotein D (gD), that had their N-terminus modified with hydrophobic moieties containing two C18 hydrocarbon chains. Pure and mixed micelles of gB and/or gD peptide epitopes were easily prepared after starting with the synthesis of corresponding PAs by solid phase methods. Structural characterization of the aggregates confirmed that they were sufficiently stable and compatible with in vivo use: critical micelle concentration values around 4.0 ⋅ 10(-7) mol ⋅ Kg(-1); hydrodynamic radii (RH) between 50-80 nm, and a zeta potential (ζ) around - 40 mV were found for all aggregates. The in vitro results indicate that both peptide epitopes and micelles, at 10 μM, triggered U937 and RAW 264.7 cells to release appreciable levels of cytokines. In particular, interleukin (IL)-23-, IL-6-, IL-8- or macrophage inflammatory protein (MIP)-2-, and tumor necrosis factor (TNF)-α-release increased considerably when cells were treated with the gB-micelles or gD-micelles compared with the production of the same cytokines when the stimulus was the single gB or gD peptide.

  6. Short Anabolic Peptides for Bone Growth.

    Science.gov (United States)

    Amso, Zaid; Cornish, Jillian; Brimble, Margaret A

    2016-07-01

    Loss of bone occurs in the age-related skeletal disorder, osteoporosis, leading to bone fragility and increased incidence of fractures, which are associated with enormous costs and substantial morbidity and mortality. Recent data indicate that osteoporotic fractures are more common than other diseases, which usually attract public attention (e.g., heart attack and breast cancer). The prevention and treatment of this skeletal disorder are therefore of paramount importance. Majority of osteoporosis medications restore skeletal balance by reducing osteoclastic activity, thereby reducing bone resorption. These agents, however, do not regenerate damaged bone tissue, leaving limited options for patients once bone loss has occurred. Recently, attention has turned to bone-anabolic agents. Such agents have the ability to increase bone mass and strength, potentially reversing structural damage. To date, only one bone-anabolic drug is available in the market. The discovery of more novel, cost-effective bone anabolic agents is therefore a priority to treat those suffering from this disabling condition. Short peptides offer an important alternative for the development of novel bone-anabolic agents given their high target binding specificity, which translates into potent activity with limited side effects. This review summarizes attempts in the identification of bone-anabolic peptides, and their development for promoting bone growth. © 2016 Wiley Periodicals, Inc.

  7. Cellular Internalization of Therapeutic Oligonucleotides by Peptide Amphiphile Nanofibers and Nanospheres.

    Science.gov (United States)

    Mumcuoglu, Didem; Sardan Ekiz, Melis; Gunay, Gokhan; Tekinay, Turgay; Tekinay, Ayse B; Guler, Mustafa O

    2016-05-11

    Oligonucleotides are promising drug candidates due to the exceptionally high specificity they exhibit toward their target DNA and RNA sequences. However, their poor pharmacokinetic and pharmacodynamic properties, in conjunction with problems associated with their internalization by cells, necessitates their delivery through specialized carrier systems for efficient therapy. Here, we investigate the effects of carrier morphology on the cellular internalization mechanisms of oligonucleotides by using self-assembled fibrous or spherical peptide nanostructures. Size and geometry were both found to be important parameters for the oligonucleotide internalization process; direct penetration was determined to be the major mechanism for the internalization of nanosphere carriers, whereas nanofibers were internalized by clathrin- and dynamin-dependent endocytosis pathways. We further showed that glucose conjugation to carrier nanosystems improved cellular internalization in cancer cells due to the enhanced glucose metabolism associated with oncogenesis, and the internalization of the glucose-conjugated peptide/oligonucleotide complexes was found to be dependent on glucose transporters present on the surface of the cell membrane.

  8. The membrane interaction of amphiphilic model peptides affects phosphatidylserine headgroup and acyl chain order and dynamics. Application of the phospholipid headgroup electrometer concept to phosphatidylserine

    International Nuclear Information System (INIS)

    de Kroon, A.I.P.M.; Killian, J.A.; de Gier, J.; de Kruijff, B.

    1991-01-01

    Deuterium nuclear magnetic resonance ( 2 H NMR) was used to study the interaction of amphiphilic model peptides with model membranes consisting of 1,2-dioleoyl-sn-glycero-3-phospho-L-serine deuterated either at the β-position of the serine moiety ([2- 2 H]DOPS) or at the 11-position of the acyl chains ([11,11- 2 H 2 ]DOPS). The peptides are derived from the sequences H-Ala-Met-Leu-Trp-Ala-OH and H-Arg-Met-Leu-Trp-Ala-OH and contain a positive charge of +1 or +2 at the amino terminus or one positive charge at each end of the molecule. Upon titration of dispersions of DOPS with the peptides, the divalent peptides show a similar extent of binding to the DOPS bilyers, which is larger than that of the single charged peptide. Under these conditions the values of the quadrupolar splitting of both [2- 2 H]DOPS and [11,11- 2 H 2 ]DOPS are decreased, indicating that the peptides reduce the order of both the DOPS headgroup and the acyl chains. The extent of the decrease depends on the amount of peptide bound and on the position of the charged moieties in the peptide molecule. Titrations of DOPS with poly(L-lysine) 100 , which were included for reasons of comparison, reveal increased Δv q values. When the peptide-lipid titrations are carried out without applying a freeze-thaw procedure to achieve full equilibration, two-component 2 H NMR spectra occur. The apparently limited accessibility of the lipid to the peptides under these circumstances is discussed in relation to the ability of the peptides to exhibit transbilayer movement. 2 H spin-lattice relaxation time T1 measurements demonstrate a decrease of the rates of motion of both headgroup and acyl chains of DOPS in the presence of the peptides

  9. Folding very short peptides using molecular dynamics.

    Directory of Open Access Journals (Sweden)

    Bosco K Ho

    2006-04-01

    Full Text Available Peptides often have conformational preferences. We simulated 133 peptide 8-mer fragments from six different proteins, sampled by replica-exchange molecular dynamics using Amber7 with a GB/SA (generalized-Born/solvent-accessible electrostatic approximation to water implicit solvent. We found that 85 of the peptides have no preferred structure, while 48 of them converge to a preferred structure. In 85% of the converged cases (41 peptides, the structures found by the simulations bear some resemblance to their native structures, based on a coarse-grained backbone description. In particular, all seven of the beta hairpins in the native structures contain a fragment in the turn that is highly structured. In the eight cases where the bioinformatics-based I-sites library picks out native-like structures, the present simulations are largely in agreement. Such physics-based modeling may be useful for identifying early nuclei in folding kinetics and for assisting in protein-structure prediction methods that utilize the assembly of peptide fragments.

  10. Sustained and controlled release of lipophilic drugs from a self-assembling amphiphilic peptide hydrogel

    DEFF Research Database (Denmark)

    Briuglia, Maria-Lucia; Urquhart, Andrew; Lamprou, Dimitrios A.

    2014-01-01

    . In this work, we have investigated the diffusion properties of Pindolol, Quinine and Timolol maleate from RADA16 in PBS and in BSS-PLUS at 37°C. A sustained, controlled, reproducible and efficient drug release has been detected for all the systems, which allows to understand the dependence of release kinetics......Materials which undergo self-assembly to form supramolecular structures can provide alternative strategies to drug loading problems in controlled release application. RADA 16 is a simple and versatile self-assembling peptide with a designed structure formed of two distinct surfaces, one hydrophilic...... and one hydrophobic that are positioned in such a well-ordered fashion allowing precise assembly into a predetermined organization. A "smart" architecture in nanostructures can represent a good opportunity to use RADA16 as a carrier system for hydrophobic drugs solving problems of drugs delivery...

  11. Aggregation properties of a short peptide that mediates amyloid fibril ...

    Indian Academy of Sciences (India)

    Short peptides have been identified from amyloidogenic proteins that form amyloid fibrils in isolation. The hexapeptide stretch 21DIDLHL26 has been shown to be important in the self-assembly of the Src homology 3 (SH3) domain of p85 subunit of bovine phosphatidylinositol-3-kinase (PI3-SH3). The SH3 domain of ...

  12. High cell selectivity and low-level antibacterial resistance of designed amphiphilic peptide G(IIKK)(3)I-NH(2).

    Science.gov (United States)

    Chen, Cuixia; Hu, Jing; Zeng, Ping; Chen, Yucan; Xu, Hai; Lu, Jian R

    2014-10-08

    On the basis of cell cultures involving bacterial strains (Escherichia coli 5α and Bacillus subtilis 168) and a mammalian cell line (NIH 3T3), the potent antibacterial activity and distinct selectivity from designed amphiphilic peptides G(IIKK)nI-NH2 (n = 2-4) have been demonstrated. This work extends these studies to multidrug resistant pathogens (ESBL-producing E. coli) and primary human cells (HDFa), followed by the in vivo mouse model investigation of ESBL-producing bacterial infection. G(IIKK)3I-NH2 exhibits high antibacterial activity against the pathogenic strain both in vitro and in vivo while displaying low toxicity toward the primary cells and the mice. Peptide molecules can kill bacteria by selectively interacting with bacterial membranes, causing structural disruptions. Furthermore, multidrug resistant ESBL-producing bacteria do not develop resistance after multiple treatments with G(IIKK)3I-NH2. The high cellular selectivity, low toxicity toward mammalian hosts and noninducing bacterial resistance indicate great potential for developing the peptides as anti-infection agents.

  13. EphA2-derived peptide vaccine with amphiphilic poly(gamma-glutamic acid) nanoparticles elicits an anti-tumor effect against mouse liver tumor.

    Science.gov (United States)

    Yamaguchi, Shinjiro; Tatsumi, Tomohide; Takehara, Tetsuo; Sasakawa, Akira; Yamamoto, Masashi; Kohga, Keisuke; Miyagi, Takuya; Kanto, Tatsuya; Hiramastu, Naoki; Akagi, Takami; Akashi, Mitsuru; Hayashi, Norio

    2010-05-01

    The prognosis of liver cancer remains poor, but recent advances in nanotechnology offer promising possibilities for cancer treatment. Novel adjuvant, amphiphilic nanoparticles (NPs) composed of L: -phenylalanine (Phe)-conjugated poly(gamma-glutamic acid) (gamma-PGA-Phe NPs) having excellent capacity for carrying peptides, were found to have the potential for use as a peptide vaccine against tumor models overexpressing artificial antigens, such as ovalbumin (OVA). However, the anti-tumor potential of gamma-PGA-Phe NPs vaccines using much less immunogenic tumor-associated antigen (TAA)-derived peptide needs to be clarified. In this study, we evaluated the effectiveness of immunization with EphA2, recently identified TAA, derived peptide-immobilized gamma-PGA-Phe NPs (Eph-NPs) against mouse liver tumor of MC38 cells (EphA2-positive colon cancer cells). Immunization of normal mice with Eph-NPs resulted in generation of EphA2-specific type-1 CD8+ T cells. Immunization with Eph-NPs tended to provide a degree of anti-MC38 liver tumor protection more than that observed for immunization with the mixture of EphA2-derived peptide and complete Freund's adjuvant (Eph + CFA). Neither Eph-NPs nor Eph + CFA vaccines inhibited tumor growth of BL6, EphA2-negative melanoma cells. Splenocytes isolated from MC38-bearing mice treated with Eph-NPs showed strong and specific cytotoxic activity against MC38 cells. Immunization with Eph + CFA induced liver damage as evidenced by elevation of serum alanine aminotransferase, while Eph-NPs vaccination did not exhibit any toxic damage to the liver. These results demonstrated that immunization with Eph-NPs displayed anti-tumor effects against liver tumor by generating acquired immunity equivalent to the toxic adjuvant CFA, suggesting that safe gamma-PGA-Phe NPs could be applied clinically for the vaccine treatment of liver cancer.

  14. Effects of solubilization of short and medium-chain molecules in the self-assembly of two amphiphilic drugs in solution

    Energy Technology Data Exchange (ETDEWEB)

    Barbosa, Silvia [Grupo de Fisica de Coloides y Polimeros, Departamento de Fisica de la Materia Condensada, Facultad de Fisica, Universidad de Santiago de Compostela (Spain)], E-mail: silvia.barbosa@usc.es; Cheema, Mohammad Arif; Siddiq, Mohammad [Department of Chemistry, Quaid-i-Azam University of Islamabad, 45320 (Pakistan); Taboada, Pablo [Grupo de Fisica de Coloides y Polimeros, Departamento de Fisica de la Materia Condensada, Facultad de Fisica, Universidad de Santiago de Compostela (Spain); Mosquera, Victor [Grupo de Fisica de Coloides y Polimeros, Departamento de Fisica de la Materia Condensada, Facultad de Fisica, Universidad de Santiago de Compostela (Spain)], E-mail: victor.mosquera@usc.es

    2009-02-15

    The effect of short and medium chain length alcohols ethanol, propanol, and butanol on the thermodynamic properties of aqueous solutions of the ionic amphiphilic antidepressants imipramine and clomipramine hydrochlorides has been investigated at T = 293 K. Critical concentrations of the drugs were obtained from ultrasound velocity measurements. Experimental results have shown a strong dependence of the ultrasound velocity with the alcohol concentration and chain length. Differences in the aggregate properties of both amphiphiles arise from the presence of the extra Cl{sup -} substituent on the ring system of clomipramine. Density and ultrasound measurements have been used to obtain the apparent molar volumes, V{sub {phi}}, and isentropic apparent molar compressibilities, K{sub {phi}}{sub (S)}, for the aqueous drug/water-alcohol solutions. The distribution coefficient of the amount solubilized between water and the aggregates, K, has been determined using an indirect method based on the pseudo-phase model by using apparent molar volume values. This method allows the calculation of the distribution coefficients at concentrations below saturation. The standard molar Gibbs free energy change on transfer from the aqueous to the micellar, {delta}G{sup 0}, phase was calculated from the partition coefficient. The results have highlighted the structural differences between both amphiphiles.

  15. Effects of solubilization of short and medium-chain molecules in the self-assembly of two amphiphilic drugs in solution

    International Nuclear Information System (INIS)

    Barbosa, Silvia; Cheema, Mohammad Arif; Siddiq, Mohammad; Taboada, Pablo; Mosquera, Victor

    2009-01-01

    The effect of short and medium chain length alcohols ethanol, propanol, and butanol on the thermodynamic properties of aqueous solutions of the ionic amphiphilic antidepressants imipramine and clomipramine hydrochlorides has been investigated at T = 293 K. Critical concentrations of the drugs were obtained from ultrasound velocity measurements. Experimental results have shown a strong dependence of the ultrasound velocity with the alcohol concentration and chain length. Differences in the aggregate properties of both amphiphiles arise from the presence of the extra Cl - substituent on the ring system of clomipramine. Density and ultrasound measurements have been used to obtain the apparent molar volumes, V φ , and isentropic apparent molar compressibilities, K φ(S) , for the aqueous drug/water-alcohol solutions. The distribution coefficient of the amount solubilized between water and the aggregates, K, has been determined using an indirect method based on the pseudo-phase model by using apparent molar volume values. This method allows the calculation of the distribution coefficients at concentrations below saturation. The standard molar Gibbs free energy change on transfer from the aqueous to the micellar, ΔG 0 , phase was calculated from the partition coefficient. The results have highlighted the structural differences between both amphiphiles

  16. The role of electrostatics and temperature on morphological transitions of hydrogel nanostructures self-assembled by peptide amphiphiles via molecular dynamics simulations.

    Science.gov (United States)

    Fu, Iris W; Markegard, Cade B; Chu, Brian K; Nguyen, Hung D

    2013-10-01

    Smart biomaterials that are self-assembled from peptide amphiphiles (PA) are known to undergo morphological transitions in response to specific physiological stimuli. The design of such customizable hydrogels is of significant interest due to their potential applications in tissue engineering, biomedical imaging, and drug delivery. Using a novel coarse-grained peptide/polymer model, which has been validated by comparison of equilibrium conformations from atomistic simulations, large-scale molecular dynamics simulations are performed to examine the spontaneous self-assembly process. Starting from initial random configurations, these simulations result in the formation of nanostructures of various sizes and shapes as a function of the electrostatics and temperature. At optimal conditions, the self-assembly mechanism for the formation of cylindrical nanofibers is deciphered involving a series of steps: (1) PA molecules quickly undergo micellization whose driving force is the hydrophobic interactions between alkyl tails; (2) neighboring peptide residues within a micelle engage in a slow ordering process that leads to the formation of β-sheets exposing the hydrophobic core; (3) spherical micelles merge together through an end-to-end mechanism to form cylindrical nanofibers that exhibit high structural fidelity to the proposed structure based on experimental data. As the temperature and electrostatics vary, PA molecules undergo alternative kinetic mechanisms, resulting in the formation of a wide spectrum of nanostructures. A phase diagram in the electrostatics-temperature plane is constructed delineating regions of morphological transitions in response to external stimuli. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. In silico study of amphiphilic nanotubes based on cyclic peptides in polar and non-polar solvent

    DEFF Research Database (Denmark)

    Vijayakumar, Vinodhkumar; Vijayaraj, Ramadoss; Peters, Günther H.J.

    2016-01-01

    The stability of cyclic peptide assemblies (CPs) forming a macromolecular nanotube structure was investigated in solvents of different polarity using computational methods. The stability and structure of the complexes were studied using traditional molecular dynamics (MD). Energy of dissociation ...

  18. Sol-gel transition behavior of aqueous peptide-amphiphile (C16-W3K) solutions: effects of alkyl-tail length, mechanical shear, temperature, and salt

    Science.gov (United States)

    Yamamoto, Masashi; Otsuka, Takahiro; Orimo, Yoshinori; Maeda, Tomoki; Hotta, Atsushi

    Peptide amphiphiles (PA) possess nanoscale micelle structures and excellent biocompatibility. In aqueous PA solution, PA molecules can self-assemble through various configurations into spherical and wormlike micelles, which can occasionally form hydrogels. C16-W3K is one of the unique PA, whose micelle configurations can transfer from spherical to wormlike structures in its aqueous solution over time, while the wormlike micelles could also lead to gelation. In our recent research, the effects of the length of the hydrophobic alkyl tail and other external factors of C16-W3K on the gelation behavior of the C16-W3K solution have been discussed. It has been revealed that longer alkyl-tails could facilitate the gelation of the C16-W3K solution, and that the external stimuli, such as mechanical shear and heat, could promote faster gelation of the C16-W3K solution. It was also found that salt could adjust the pH of the C16-W3K solution, having profound influence on the gelation behavior of the C16-W3K solution. In fact, the gelation of the C16-W3K with a higher storage modulus could be obtained from relatively acidic solutions, while the gelation of the C16-W3K solution was firmly suppressed in highly basic solutions. This work was supported by a Grant-in-Aid for Scientific Research (A) (No. 15H02298 to A.H.) and a Grant-in-Aid for Research Activity Start-up (No.15H06586 to T.M.) from JSPS: KAKENHI.

  19. Hydrophobicity drives the cellular uptake of short cationic peptide ligands.

    Science.gov (United States)

    Gupta, Anju; Mandal, Deendayal; Ahmadibeni, Yousef; Parang, Keykavous; Bothun, Geoffrey

    2011-06-01

    Short cationic linear peptide analogs (LPAs, prepared as Arg-C( n )-Arg-C( n )-Lys, where C( n ) represents an alkyl linkage with n = 4, 7 or 11) were synthesized and tested in human breast carcinoma BT-20 and CCRF-CEM leukemia cells for their application as targeting ligands. With constant LPA charge (+4), increasing the alkyl linkage increases the hydrophobic/hydrophilic balance and provides a systematic means of examining combined electrostatic and hydrophobic peptide-membrane interactions. Fluorescently conjugated LPA-C(11) (F-LPA-C(11)) demonstrated significant uptake, whereas there was negligible uptake of the shorter LPAs. By varying temperature (4°C and 37°C) and cell type, the results suggest that LPA-C(11) internalization is nonendocytic and nonspecific. The effect of LPA binding on the phase behavior, structure, and permeability of model membranes composed of dipalmitoylphosphatidylcholine and dipalmitoylphosphatidylserine (DPPC/DPPS, 85/15) was studied using differential scanning calorimetry (DSC), cryogenic transmission electron microscopy (cryo-TEM), and fluorescence leakage studies to gain insight into the LPA uptake mechanism. While all LPAs led to phase separation, LPA-C(11), possessing the longest alkyl linkage, was able to penetrate into the bilayer and caused holes to form, which led to membrane disintegration. This was confirmed by rapid and complete dye release by LPA-C(11). We propose that LPA-C(11) achieves uptake by anchoring to the membrane via hydrophobicity and forming transient membrane voids. LPAs may be advantageous as drug transporter ligands because they are small, water soluble, and easy to prepare.

  20. Design and expression of a short peptide as an HIV detection probe

    Energy Technology Data Exchange (ETDEWEB)

    Lines, Jamie A.; Yu, Zhiqiang; Dedkova, Larisa M.; Chen, Shengxi, E-mail: shengxi.chen.1@asu.edu

    2014-01-03

    Highlights: •We designed a short fusion peptide (FP-50) for in vivo expression. •This peptide is a very promising component for detection of gp120 protein. •The detectable level is about 20–200 times lower than previously published methods. •It is a novel probe to detect HIV-1 gp120 during early stages of HIV infection. -- Abstract: To explore a low-cost novel probe for HIV detection, we designed and prepared a 50-amino acid-length short fusion peptide (FP-50) via Escherichia coli in vivo expression. It was employed as a novel probe to detect HIV-1 gp120 protein. The detectable level of gp120 protein using the FP-50 peptide was approximately 20–200 times lower than previously published methods that used a pair of monoclonal antibodies. Thus, this short peptide is a very promising component for detection of gp120 protein during early stages of HIV infection.

  1. In vitro determination of the short-chain synthetic peptide RP13 antimicrobial activity.

    Science.gov (United States)

    Sánchez, Adrián; Calderón, Ernesto; Castañón-Alonso, Sandra L; Santos, Araceli; Hernández, Beatriz; Vázquez, Alfredo

    2014-01-01

    The proliferation of antibiotic-resistant microorganisms, along with the lack of new drugs against them, has elicited the interest of the scientific community on the study and development of endogenous synthetic compounds with bacteriostatic or bactericidal activity. In recent years, several short-chain, low molecular weight peptides isolated from natural sources such as plants and animals have demonstrated an array of antimicrobial activities. Despite having structural characteristics similar to microbicidal peptides isolated from human platelets, peptide RP11 does not exhibit antimicrobial activity. In vitro determination of the antimicrobial activity of the synthetic peptide RP13. Peptide RP13 was prepared modifying the original amino acids sequence of peptide RP11, reversing the position of the amino acids lysine and tyrosine in order to modify the conformation of the original peptide. These amino acids are localized close to the N-terminus of the peptidic chain. Peptide RP13 was prepared in solution using conventional methods for peptide synthesis. The antimicrobial activity of RP13 was assessed against the microorganisms S. aureus, E. faecalis and E. coli in a test solution and later evaluated by cultivation of plates during the first 2 h after inoculation of bacteria. RP13 activity antimicrobial was compared against tetracycline, a broad-spectrum antibiotic. The new peptide RP13, resulting form the structural modification of the amino acid sequence of peptide RP11, displayed antimicrobial activity. RP13 demonstrated to be more efficient inhibiting the growth of gram-positive than gramnegative bacteria. The structural modification of peptide RP11, obtained from human platelets, resulted in a new peptide with improved antimicrobial activity. These results clearly demonstrate that peptides of natural origin, as well as their synthetic analogs, represent an attractive alternative against pathogenic agents.

  2. Modulating short tryptophan- and arginine-rich peptides activity by substitution with histidine.

    Science.gov (United States)

    Bacalum, Mihaela; Janosi, Lorant; Zorila, Florina; Tepes, Ana-Maria; Ionescu, Cristina; Bogdan, Elena; Hadade, Niculina; Craciun, Liviu; Grosu, Ion; Turcu, Ioan; Radu, Mihai

    2017-07-01

    High antimicrobial efficacy of short tryptophan-and arginine-rich peptides makes them good candidates in the fight against pathogens. Substitution of tryptophan and arginine by histidine could be used to modulate the peptides efficacy by optimizing their structures. The peptide (RRWWRWWRR), reported to showed good antimicrobial efficacy, was used as template, seven new analogs being designed substituting tryptophan or arginine with histidine. The peptides' efficacy was tested against E. coli, B. subtilis and S. aureus. The cytotoxicity and hemolytic effect were evaluated and the therapeutic index was inferred for each peptide. Atomic force microscopy and molecular simulation were used to analyze the effects of peptides on bacterial membrane. The substitution of tryptophan by histidine proved to strongly modulate the antimicrobial activity, mainly by changing the peptide-to-membrane binding energy. The substitution of arginine has low effect on the antimicrobial efficacy. The presence of histidine residue reduced the cytotoxic and hemolytic activity of the peptides in some cases maintaining the same efficacy against bacteria. The peptides' antimicrobial activity was correlated to the 3D-hydrophobic moment and to a simple structure-based packing parameter. The results show that some of these peptides have the potential to become good candidates to fight against bacteria. The substitution by histidine proved to fine tune the therapeutic index allowing the optimization of the peptide structure mainly by changing its binding energy and 3D-hydrophobic moment. The short tryptophan reach peptides therapeutic index can be maximized using the histidine substitution to optimize their structure. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Purification of a novel antibacterial short peptide in earthworm Eisenia foetida.

    Science.gov (United States)

    Liu, Yan-Qin; Sun, Zhen-Jun; Wang, Chong; Li, Shi-Jie; Liu, Yu-Zhi

    2004-04-01

    A novel antimicrobial short peptide was purified from earthworm (Eisenia foetida) by a five-step protocol including ammonium sulfate precipitation, ultrafiltration, DE-52 ion exchange chromatography, Sephadex G-10 column chromatography, and C-18 reversed-phase HPLC techniques. The purified peptide was applied to the MALDI-TOP MS to determine the molecular mass and was also subjected to TOF MS-MS analysis to determine the amino acid sequence. As a result, a novel antibacterial peptide, named OEP3121, was obtained, with the molecular mass of 510.8 Da and the sequence being "ACSAG".

  4. Short term aerobic exercise training increases postprandial pancreatic polypeptide but not peptide YY concentrations in obese individuals

    OpenAIRE

    Kanaley, Jill A.; Heden, Timothy D.; Liu, Ying; Whaley-Connell, Adam T.; Chockalingam, Anand; Dellsperger, Kevin C.; Fairchild, Timothy J.

    2013-01-01

    Objective Short-term exercise training improves glycemic control, but the effect of short-term training on postprandial satiety peptide responses or perceived satiety remains unknown. We tested the hypothesis that short-term aerobic exercise training (15 days) would alter postprandial pancreatic and gut peptide [pancreatic polypeptide (PP) and peptide YY (PYY)] responses and perceived appetite and satiety in obese individuals. Subjects Thirteen healthy obese men and women (age: 42±2 y; BMI: 3...

  5. Computational and experimental analysis of short peptide motifs for enzyme inhibition.

    Directory of Open Access Journals (Sweden)

    Jinglin Fu

    Full Text Available The metabolism of living systems involves many enzymes that play key roles as catalysts and are essential to biological function. Searching ligands with the ability to modulate enzyme activities is central to diagnosis and therapeutics. Peptides represent a promising class of potential enzyme modulators due to the large chemical diversity, and well-established methods for library synthesis. Peptides and their derivatives are found to play critical roles in modulating enzymes and mediating cellular uptakes, which are increasingly valuable in therapeutics. We present a methodology that uses molecular dynamics (MD and point-variant screening to identify short peptide motifs that are critical for inhibiting β-galactosidase (β-Gal. MD was used to simulate the conformations of peptides and to suggest short motifs that were most populated in simulated conformations. The function of the simulated motifs was further validated by the experimental point-variant screening as critical segments for inhibiting the enzyme. Based on the validated motifs, we eventually identified a 7-mer short peptide for inhibiting an enzyme with low μM IC50. The advantage of our methodology is the relatively simplified simulation that is informative enough to identify the critical sequence of a peptide inhibitor, with a precision comparable to truncation and alanine scanning experiments. Our combined experimental and computational approach does not rely on a detailed understanding of mechanistic and structural details. The MD simulation suggests the populated motifs that are consistent with the results of the experimental alanine and truncation scanning. This approach appears to be applicable to both natural and artificial peptides. With more discovered short motifs in the future, they could be exploited for modulating biocatalysis, and developing new medicine.

  6. Short Peptides Enhance Single Cell Adhesion and Viability onMicroarrays

    Energy Technology Data Exchange (ETDEWEB)

    Veiseh, Mandana; Veiseh, Omid; Martin, Michael C.; Asphahani,Fareid; Zhang, Miqin

    2007-01-19

    Single cell patterning holds important implications forbiology, biochemistry, biotechnology, medicine, and bioinformatics. Thechallenge for single cell patterning is to produce small islands hostingonly single cells and retaining their viability for a prolonged period oftime. This study demonstrated a surface engineering approach that uses acovalently bound short peptide as a mediator to pattern cells withimproved single cell adhesion and prolonged cellular viabilityon goldpatterned SiO2 substrates. The underlying hypothesis is that celladhesion is regulated bythe type, availability, and stability ofeffective cell adhesion peptides, and thus covalently bound shortpeptides would promote cell spreading and, thus, single cell adhesion andviability. The effectiveness of this approach and the underlyingmechanism for the increased probability of single cell adhesion andprolonged cell viability by short peptides were studied by comparingcellular behavior of human umbilical cord vein endothelial cells on threemodelsurfaces whose gold electrodes were immobilized with fibronectin,physically adsorbed Arg-Glu-Asp-Val-Tyr, and covalently boundLys-Arg-Glu-Asp-Val-Tyr, respectively. The surface chemistry and bindingproperties were characterized by reflectance Fourier transform infraredspectroscopy. Both short peptides were superior to fibronectin inproducing adhesion of only single cells, whereas the covalently boundpeptide also reduced apoptosis and necrosisof adhered cells. Controllingcell spreading by peptide binding domains to regulate apoptosis andviability represents a fundamental mechanism in cell-materialsinteraction and provides an effective strategy in engineering arrays ofsingle cells.

  7. SFA-SPA: a suffix array based short peptide assembler for metagenomic data.

    Science.gov (United States)

    Yang, Youngik; Zhong, Cuncong; Yooseph, Shibu

    2015-06-01

    The determination of protein sequences from a metagenomic dataset enables the study of metabolism and functional roles of the organisms that are present in the sampled microbial community. We had previously introduced algorithm and software for the accurate reconstruction of protein sequences from short peptides identified on nucleotide reads in a metagenomic dataset. Here, we present significant computational improvements to the short peptide assembly algorithm that make it practical to reconstruct proteins from large metagenomic datasets containing several hundred million reads, while maintaining accuracy. The improved computational efficiency is achieved using a suffix array data structure that allows for fast querying during the assembly process, and a significant redesign of assembly steps that enables multi-threaded execution. The program is available under the GPLv3 license from sourceforge.net/projects/spa-assembler. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  8. A short synthetic peptide fragment of human C2ORF40 has therapeutic potential in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Chaoyang [Shandong Univ., Jinan (China); Zhang, Pengju [Shandong Univ., Jinan (China); Jiang, Anli [Shandong Univ., Jinan (China); Mao, Jian-Hua [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Wei, Guangwei [Shandong Univ. School of Medicine, Jinan (China)

    2017-03-30

    C2ORF40 encodes a secreted protein which is cleaved to generate soluble peptides by proteolytic processing and this process is believed to be necessary for C2ORF40 to exert cell type specific biological activity. Here, we reported a short mimic peptide of human C2ORF40 acts potential therapeutic efficacy in human cancer cells in vitro and in vivo. We synthesized a short peptide of human C2ORF40, named C2ORF40 mimic peptide fragment and assessed its biological function on cancer cell growth, migration and tumorigenesis. Cell growth assay showed that C2ORF40 mimic peptide fragment significantly suppressed cell proliferation of breast and lung cancer cells. Moreover, C2ORF40 mimic peptide fragment significantly inhibited the migration and invasion of breast cancer cells. Furthermore, we showed that this peptide suppressed tumorigenesis in breast tumor xenograft model. Cell cycle assay indicated that the C2ORF40 mimic peptide fragment suppressed the growth of tumor cells through inducing mitotic phase arrest. In conclusion, our results firstly suggested that this short synthetic peptide of human C2ORF40 may be a candidate tumor therapeutic agent.

  9. A short synthetic peptide fragment of human C2ORF40 has therapeutic potential in breast cancer.

    Science.gov (United States)

    Li, Chaoyang; Zhang, Pengju; Jiang, Anli; Mao, Jian-Hua; Wei, Guangwei

    2017-06-27

    C2ORF40 encodes a secreted protein which is cleaved to generate soluble peptides by proteolytic processing and this process is believed to be necessary for C2ORF40 to exert cell type specific biological activity. Here, we reported a short mimic peptide of human C2ORF40 acts potential therapeutic efficacy in human cancer cells in vitro and in vivo. We synthesized a short peptide of human C2ORF40, named C2ORF40 mimic peptide fragment and assessed its biological function on cancer cell growth, migration and tumorigenesis. Cell growth assay showed that C2ORF40 mimic peptide fragment significantly suppressed cell proliferation of breast and lung cancer cells. Moreover, C2ORF40 mimic peptide fragment significantly inhibited the migration and invasion of breast cancer cells. Furthermore, we showed that this peptide suppressed tumorigenesis in breast tumor xenograft model. Cell cycle assay indicated that the C2ORF40 mimic peptide fragment suppressed the growth of tumor cells through inducing mitotic phase arrest. In conclusion, our results firstly suggested that this short synthetic peptide of human C2ORF40 may be a candidate tumor therapeutic agent.

  10. In vitro effect on Cryptosporidium parvum of short-term exposure to cathelicidin peptides.

    Science.gov (United States)

    Giacometti, Andrea; Cirioni, Oscar; Del Prete, Maria Simona; Skerlavaj, Barbara; Circo, Raffaella; Zanetti, Margherita; Scalise, Giorgio

    2003-04-01

    Two laboratory methods, a cell culture system and double fluorogenic staining, were used to study the viability and infective ability of Cryptosporidium parvum sporozoites and oocysts after short-term exposure to four cathelicidin peptides. The compounds, SMAP-29, BMAP-28, PG-1 and Bac7(1-35), exerted a strong cytotoxic effect on sporozoites, but did not affect the viability and function of oocysts consistently. Overall, in the sporozoite series, a percentage of the viable population decreased rapidly to less than detectable levels after 15 and 60 min exposure to the peptides at concentrations of 100 and 10 micro g/mL, respectively. In the oocyst series, no compound produced complete inhibition of parasite growth: 60-85% of the oocyst population was viable after 180 min exposure at 100 micro g/mL. SMAP-29 exerted the highest activity against both sporozoites and oocysts.

  11. [Screening of specific IgE-binding epitopes of dust mite allergens using short peptide array].

    Science.gov (United States)

    Teng, Feixiang; Sun, Jinxia; Wang, Nan; Yu, Lili; Cui, Yubao

    2017-08-01

    Objective To screen the possible linear epitopes of major and mid-potency allergens in Dermatophagoides farinae (Der f1, Der f2, Der f4, Der f5 and Der f7). Methods Short peptides were synthesized on the basis of the amino acid sequences in active fraction of Der f1, Der f2, Der f4, Der f5 and Der f7. Each peptide had eight amino acids in length and seven of them were overlapped with each other. Put these peptides to the chip to build microarrays that would have immunoreaction with human serum IgE. Then the chips were scanned to analyze the data. Results A total of 1128 short peptides from the above five groups of allergens were synthesized, and the microarray chips were constructed. Six serum samples from children who were allergic to Dermatophagoides farinae were mixed and added to the microarray chips. The chips were scanned and analyzed, and the results showed that Der f1 had four epitopes (46-53aa, 71-78aa, 99-110aa and 179-186aa), that Der f2 had three epitopes (15-22aa, 80-89aa and 106-113aa), that Der f 4 had six epitopes (69-82aa, 107-116aa, 225-232aa, 261-268aa, 355-365aa and 483-496aa), that Der f5 had one epitope (102-109aa), and Der f7 had three epitopes (32-39aa, 52-64aa and 100-107aa). Conclusion We identified the linear epitopes of Der f1, Der f2, Der f4, Der f5 and Der f7.

  12. Amphiphilic building blocks for self-assembly: from amphiphiles to supra-amphiphiles.

    Science.gov (United States)

    Wang, Chao; Wang, Zhiqiang; Zhang, Xi

    2012-04-17

    The process of self-assembly spontaneously creates well-defined structures from various chemical building blocks. Self-assembly can include different levels of complexity: it can be as simple as the dimerization of two small building blocks driven by hydrogen bonding or as complicated as a cell membrane, a remarkable supramolecular architecture created by a bilayer of phospholipids embedded with functional proteins. The study of self-assembly in simple systems provides a fundamental understanding of the driving forces and cooperativity behind these processes. Once the rules are understood, these guidelines can facilitate the research of highly complex self-assembly processes. Among the various components for self-assembly, an amphiphilic molecule, which contains both hydrophilic and hydrophobic parts, forms one of the most powerful building blocks. When amphiphiles are dispersed in water, the hydrophilic component of the amphiphile preferentially interacts with the aqueous phase while the hydrophobic portion tends to reside in the air or in the nonpolar solvent. Therefore, the amphiphiles aggregate to form different molecular assemblies based on the repelling and coordinating forces between the hydrophilic and hydrophobic parts of the component molecules and the surrounding medium. In contrast to conventional amphiphiles, supra-amphiphiles are constructed on the basis of noncovalent interactions or dynamic covalent bonds. In supra-amphiphiles, the functional groups can be attached to the amphiphiles by noncovalent synthesis, greatly speeding their construction. The building blocks for supra-amphiphiles can be either small organic molecules or polymers. Advances in the development of supra-amphiphiles will not only enrich the family of conventional amphiphiles that are based on covalent bonds but will also provide a new kind of building block for the preparation of complex self-assemblies. When polymers are used to construct supra-amphiphiles, the resulting

  13. Adsorption of biomedical coating molecules, amino acids, and short peptides on magnetite (110)

    Science.gov (United States)

    Aschauer, Ulrich; Selloni, Annabella

    2015-07-01

    Superparamagnetic iron oxide nanoparticles for biomedical applications are usually coated with organic molecules to form a steric barrier against agglomeration. The stability of these coatings is well established in the synthesis medium but is more difficult to assess in physiological environment. To obtain a first theoretical estimate of their stability in such an environment, we perform density functional theory calculations of the adsorption of water, polyvinyl alcohol (PVA) and polyethylene glycol (PEG) coating molecules, as well as the monomer and dimer of glycine as a prototype short peptide, on the (110) surface of magnetite (Fe3O4) in vacuo. Our results show that PVA binds significantly stronger to the surface than both PEG and glycine, while the difference between the latter two is quite small. Depending on the coverage, the water adsorption strength is intermediate between PVA and glycine. Due to its strongly interacting OH side groups, PVA is likely to remain bound to the surface in the presence of short peptides. This stability will have to be further assessed by molecular dynamics in the solvated state for which the present work forms the basis.

  14. Short, Synthetic Cationic Peptides Have Antibacterial Activity against Mycobacterium smegmatis by Forming Pores in Membrane and Synergizing with Antibiotics.

    Science.gov (United States)

    Gupta, Kajal; Singh, Sameer; van Hoek, Monique L

    2015-08-24

    Multicellular organisms are constantly exposed to a multitude of pathogenic microbes. Infection is inhibited in vivo by the innate and adaptive immune system. Mycobacterium species have emerged that are resistant to most antibiotics. We identified several naturally occurring cationic antimicrobial peptides that were active at low micromolar concentrations against Mycobacterium smegmatis. Human-derived cathelicidin LL-37 is well characterized and studied against M. smegmatis; we compared LL-37 with Chinese cobra-derived cathelicidin NA-CATH and mouse cathelicidin (mCRAMP). Two synthetic 11-residue peptides (ATRA-1A and ATRA-2) containing variations of a repeated motif within NA-CATH were tested for their activity against M. smegmatis along with a short synthetic peptide derivative from the human beta-defensin hBD3 (hBD3-Pep4). We hypothesized that these smaller synthetic peptides may demonstrate antimicrobial effectiveness with shorter length (and at less cost), making them strong potential candidates for development into broad-spectrum antimicrobial compounds or use in combination with antibiotics. These peptides have antimicrobial activity with EC50 ranging from 0.05 to 1.88 μg/mL against Mycobacterium smegmatis. The ATRA-1A short peptide was found to be the most effective antimicrobial peptide (AMP) (EC50 = 0.05 μg/mL). High bactericidal activity correlated with bacterial membrane depolarization and permeabilization activities. The efficacy of the peptides was further analyzed through Minimal Inhibitory Concentration (MIC) assays. The MICs were determined by the microdilution method. The peptide mCRAMP showed the best MIC activity at 15.6 μg/mL. Neither of the effective short synthetic peptides demonstrated synergy with the antibiotic rifampicin, although both demonstrated synergy with the cyclic peptide antibiotic polymyxin B. The peptides LL-37 and mCRAMP displayed synergism with rifampicin in MIC assays, whereas antibiotic polymyxin B displayed synergism

  15. Short, Synthetic Cationic Peptides Have Antibacterial Activity against Mycobacterium smegmatis by Forming Pores in Membrane and Synergizing with Antibiotics

    Directory of Open Access Journals (Sweden)

    Kajal Gupta

    2015-08-01

    Full Text Available Multicellular organisms are constantly exposed to a multitude of pathogenic microbes. Infection is inhibited in vivo by the innate and adaptive immune system. Mycobacterium species have emerged that are resistant to most antibiotics. We identified several naturally occurring cationic antimicrobial peptides that were active at low micromolar concentrations against Mycobacterium smegmatis. Human-derived cathelicidin LL-37 is well characterized and studied against M. smegmatis; we compared LL-37 with Chinese cobra-derived cathelicidin NA-CATH and mouse cathelicidin (mCRAMP. Two synthetic 11-residue peptides (ATRA-1A and ATRA-2 containing variations of a repeated motif within NA-CATH were tested for their activity against M. smegmatis along with a short synthetic peptide derivative from the human beta-defensin hBD3 (hBD3-Pep4. We hypothesized that these smaller synthetic peptides may demonstrate antimicrobial effectiveness with shorter length (and at less cost, making them strong potential candidates for development into broad-spectrum antimicrobial compounds or use in combination with antibiotics. These peptides have antimicrobial activity with EC50 ranging from 0.05 to 1.88 μg/mL against Mycobacterium smegmatis. The ATRA-1A short peptide was found to be the most effective antimicrobial peptide (AMP (EC50 = 0.05 μg/mL. High bactericidal activity correlated with bacterial membrane depolarization and permeabilization activities. The efficacy of the peptides was further analyzed through Minimal Inhibitory Concentration (MIC assays. The MICs were determined by the microdilution method. The peptide mCRAMP showed the best MIC activity at 15.6 μg/mL. Neither of the effective short synthetic peptides demonstrated synergy with the antibiotic rifampicin, although both demonstrated synergy with the cyclic peptide antibiotic polymyxin B. The peptides LL-37 and mCRAMP displayed synergism with rifampicin in MIC assays, whereas antibiotic polymyxin B displayed

  16. Short-term administration of glucagon-like peptide-2. Effects on bone mineral density and markers of bone turnover in short-bowel patients with no colon

    DEFF Research Database (Denmark)

    Haderslev, K V; Jeppesen, P B; Hartmann, B

    2002-01-01

    Glucagon-like peptide 2 (GLP-2) is a newly discovered intestinotrophic hormone. We have recently reported that a 5-week GLP-2 treatment improved the intestinal absorptive capacity of short-bowel patients with no colon. Additionally, GLP-2 treatment was associated with changes in body composition ...

  17. A short circulating peptide nanofiber as a carrier for tumoral delivery.

    Science.gov (United States)

    Wagh, Anil; Singh, Jagdish; Qian, Steven; Law, Benedict

    2013-05-01

    The cellular interactions and in vivo distribution of the nanomaterials are known to be strongly influenced by their physiochemical properties. Here, we investigated and compared the biocompatibility, pharmacokinetics, and biodistribution of previously reported peptide-based nanofiber (NFP), with commercially available nanomaterials. The NFP was a 2-dimensional (2D) structure with an extremely narrow width (4 nm) and a controllable length (50 to 400 nm). NFP was found to be non-toxic, hemocompatible, and with a minimum uptake by macrophages. In vivo studies further demonstrated that NFP could be delivered to the tumor site more effectively, and within a very shorter period of time, than spherical nanoparticles. Importantly, the undelivered NFP was rapidly eliminated by renal clearance and, thus, avoiding its accumulation in the spleen or liver. Overall, our data suggested a new paradigm in drug delivery via using a short circulating NFP, rather than a long circulating 3D nanoparticle, as a delivery cargo. In this study, the role of small peptide-based nanocarriers is investigated for tumor-specific delivery, reporting excellent targeting properties and a favorable toxicity profile. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Genetically encoded short peptide tag for versatile protein labeling by Sfp phosphopantetheinyl transferase.

    Science.gov (United States)

    Yin, Jun; Straight, Paul D; McLoughlin, Shaun M; Zhou, Zhe; Lin, Alison J; Golan, David E; Kelleher, Neil L; Kolter, Roberto; Walsh, Christopher T

    2005-11-01

    An 11-residue peptide with the sequence DSLEFIASKLA was identified from a genomic library of Bacillus subtilis by phage display as an efficient substrate for Sfp phosphopantetheinyl transferase-catalyzed protein labeling by small molecule-CoA conjugates. We name this peptide the "ybbR tag," because part of its sequence is derived from the ybbR ORF in the B. subtilis genome. The site of Sfp-catalyzed ybbR tag labeling was mapped to the underlined Ser residue, and the ybbR tag was found to have a strong tendency for adopting an alpha-helical conformation in solution. Here we demonstrate that the ybbR tag can be fused to the N or C termini of target proteins or inserted in a flexible loop in the middle of a target protein for site-specific protein labeling by Sfp. The short size of the ybbR tag and its compatibility with various target proteins, the broad substrate specificity of Sfp for labeling the ybbR tag with small-molecule probes of diverse structures, and the high specificity and efficiency of the labeling reaction make Sfp-catalyzed ybbR tag labeling an attractive tool for expanding protein structural and functional diversities by posttranslational modification.

  19. Short peptide based nanotubes capable of effective curcumin delivery for treating drug resistant malaria.

    Science.gov (United States)

    Alam, Shadab; Panda, Jiban Jyoti; Mukherjee, Tapan Kumar; Chauhan, Virander Singh

    2016-04-05

    Curcumin (Ccm) has shown immense potential as an antimalarial agent; however its low solubility and less bioavailability attenuate the in vivo efficacy of this potent compound. In order to increase Ccm's bioavailability, a number of organic/inorganic polymer based nanoparticles have been investigated. However, most of the present day nano based delivery systems pose a conundrum with respect to their complex synthesis procedures, poor in vivo stability and toxicity issues. Peptides due to their high biocompatibility could act as excellent materials for the synthesis of nanoparticulate drug delivery systems. Here, we have investigated dehydrophenylalanine (ΔPhe) di-peptide based self-assembled nanoparticles for the efficient delivery of Ccm as an antimalarial agent. The self-assembly and curcumin loading capacity of different ΔPhe dipeptides, phenylalanine-α,β-dehydrophenylalanine (FΔF), arginine-α,β-dehydrophenylalanine (RΔF), valine-α,β-dehydrophenylalanine (VΔF) and methonine-α,β-dehydrophenylalanine (MΔF) were investigated for achieving enhanced and effective delivery of the compound for potential anti-malarial therapy. FΔF, RΔF, VΔF and MΔF peptides formed different types of nanoparticles like nanotubes and nanovesicles under similar assembling conditions. Out of these, F∆F nanotubes showed maximum curcumin loading capacity of almost 68 % W/W. Ccm loaded F∆F nanotubes (Ccm-F∆F) showed comparatively higher (IC50, 3.0 µM) inhibition of Plasmodium falciparum (Indo strain) as compared to free Ccm (IC50, 13 µM). Ccm-F∆F nano formulation further demonstrated higher inhibition of parasite growth in malaria infected mice as compared to free Ccm. The dipeptide nanoparticles were highly biocompatible and didn't show any toxic effect on mammalian cell lines and normal blood cells. This work provides a proof of principle of using highly biocompatible short peptide based nanoparticles for entrapment and in vivo delivery of Ccm leading to an

  20. The impact of α-hydrazino acids embedded in short fluorescent peptides on peptide interactions with DNA and RNA.

    Science.gov (United States)

    Suć, Josipa; Tumir, Lidija-Marija; Glavaš-Obrovac, Ljubica; Jukić, Marijana; Piantanida, Ivo; Jerić, Ivanka

    2016-06-07

    A series of novel hydrazino-based peptidomimetics and analogues comprising N-terminal lysine and C-terminal phenanthridinyl-l-alanine were prepared. The presented results demonstrate the up to now unknown possibility to finely modulate peptide interactions with DNA/RNA by α-hydrazino group insertion and how the different positioning of two α-hydrazino groups in peptides controls binding to various double stranded and single stranded DNA and RNA. All peptidomimetics bind with 1-10 micromolar affinity to ds-DNA/RNA, whereby the binding mode is a combination of electrostatic interactions and hydrophobic interactions within DNA/RNA grooves. Insertion of the α-hydrazino group into the peptide systematically decreased its fluorimetric response to DNA/RNA binding in the order: mono-hydrazino < alternating-hydrazino < sequential-hydrazino group. Binding studies of ss-polynucleotides suggest intercalation of phenanthridine between polynucleotide bases, whereby affinity and fluorimetric response decrease with the number of α-hydrazino groups in the peptide sequence. Particularly interesting was the interaction of two sequential α-hydrazino acids-peptidomimetic with poly rG, characterised by a specific strong increase of CD bands, while all other peptide/ssRNA combinations gave only a CD-band decrease. All mentioned interactions could also be reversibly controlled by adjusting the pH, due to the protonation of the fluorophore.

  1. Effect of positively charged short peptides on stability of cubic phases of monoolein/dioleoylphosphatidic acid mixtures.

    Science.gov (United States)

    Masum, Shah Md; Li, Shu Jie; Awad, Tarek S; Yamazaki, Masahito

    2005-06-07

    To elucidate the stability and phase transition of cubic phases of biomembranes with infinite periodic minimal surface is indispensable from biological and physicochemical aspects. In this report, we investigated the effect of positively charged peptide-3K (LLKKK) and poly(L-lysine) on the phase stability of monoolein (MO) membranes containing negatively charged dioleoylphosphatidic acid (DOPA) (i.e., DOPA/MO membranes) using small-angle X-ray scattering. At first, the effect of peptide-3K on 10% DOPA/90% MO membrane in excess water, which is in the Q229 phase, was investigated. At 3.4 mM peptide-3K, a Q229 to Q230 phase transition occurred, and at >3.4 mM peptide-3K, the membrane was in the Q230 phase. Poly(L-lysine) (M(w) 1K-4K) also induced the Q230 phase, but peptide-2K (LLKK) could not induce it in the same membrane. We also investigated the effect of peptide-3K on the multilamellar vesicle (MLV) of 25% DOPA/75% MO membrane, which is in L(alpha) phase. In the absence of peptide, the spacing of MLV was very large (11.3 nm), but at > or = 8 mM peptide-3K, it greatly decreased to a constant value (5.2 nm), irrespective of the peptide concentration, indicating that peptide-3K and the membranes form an electrostatically stabilized aggregation with low water content. Poly(L-lysine) also decreased greatly the spacing of the 25% DOPA/75% MO MLV, indicating the formation of a similar aggregation. To compare the effects of peptide-3K and poly(L-lysine) with that of osmotic stress on stability of the cubic phase, we investigated the effect of poly(ethylene glycol) with molecular weight 7500 (PEG-6K) on the phase stability of 10% DOPA/90% MO membrane. With an increase in PEG-6K concentration, i.e., with an increase in osmotic stress, the most stable phase changed as follows; Q229 (Schwartz's P surface) --> Q224 (D) --> Q230 (G). On the basis of these results, we discuss the mechanism of the effects of the positively charged short peptides (peptide-3K) and poly

  2. Membrane anchorage brings about fusogenic properties in a short synthetic peptide

    NARCIS (Netherlands)

    Pecheur, EI; Hoekstra, D; SainteMarie, J; Maurin, L; Bienvenue, A; Philippot, [No Value

    1997-01-01

    The fusogenic properties of an amphipathic net-negative peptide (wae 11), consisting of 11 amino acid residues, were studied. We demonstrate that, whereas the free peptide displays no significant fusion activity, membrane fusion is strongly promoted when the peptide is anchored to a liposomal

  3. pH-dependent and pH-independent self-assembling behavior of surfactant-like peptides

    DEFF Research Database (Denmark)

    Gurevich, Leonid; Fojan, Peter

    2012-01-01

    Self-assembly of amphiphilic peptides designed during the last years by several research groups leads to a large variety of 3D-structures that already found applications in stabilization of large protein complexes, cell culturing systems etc. In this report, we present synthesis and characterizat......Self-assembly of amphiphilic peptides designed during the last years by several research groups leads to a large variety of 3D-structures that already found applications in stabilization of large protein complexes, cell culturing systems etc. In this report, we present synthesis...... and characterization of two novel families of amphiphilic peptides KAn and KAnW (n=6,5,4) that exhibits clear charge separation controllable by pH of the environment. As the pH changes from acidic to basic, the charge on the ends of the peptide molecule varies eventually leading to reorganization of KAn micelles...... formation of ordered aggregates with well-defined secondary structure from short unstructured peptides and provide a simple system where factors responsible for self-assembly can be singled out and studied one by one. The ability to control the shape and structure of peptide aggregates can provide basis...

  4. Modulation of intra- and inter-sheet interactions in short peptide self-assembly by acetonitrile in aqueous solution

    International Nuclear Information System (INIS)

    Deng Li; Zhao Yurong; Zhou Peng; Xu Hai; Wang Yanting

    2016-01-01

    Besides our previous experimental discovery (Zhao Y R, et al . 2015 Langmuir , 31, 12975) that acetonitrile (ACN) can tune the morphological features of nanostructures self-assembled by short peptides KIIIIK (KI4K) in aqueous solution, further experiments reported in this work demonstrate that ACN can also tune the mass of the self-assembled nanostructures. To understand the microscopic mechanism how ACN molecules interfere peptide self-assembly process, we conducted a series of molecular dynamics simulations on a monomer, a cross- β sheet structure, and a proto-fibril of KI4K in pure water, pure ACN, and ACN-water mixtures, respectively. The simulation results indicate that ACN enhances the intra-sheet interaction dominated by the hydrogen bonding (H-bonding) interactions between peptide backbones, but weakens the inter-sheet interaction dominated by the interactions between hydrophobic side chains. Through analyzing the correlations between different groups of solvent and peptides and the solvent behaviors around the proto-fibril, we have found that both the polar and nonpolar groups of ACN play significant roles in causing the opposite effects on intermolecular interactions among peptides. The weaker correlation of the polar group of ACN than water molecule with the peptide backbone enhances H-bonding interactions between peptides in the proto-fibril. The stronger correlation of the nonpolar group of ACN than water molecule with the peptide side chain leads to the accumulation of ACN molecules around the proto-fibril with their hydrophilic groups exposed to water, which in turn allows more water molecules close to the proto-fibril surface and weakens the inter-sheet interactions. The two opposite effects caused by ACN form a microscopic mechanism clearly explaining our experimental observations. (paper)

  5. Short, multiple-stranded β-hairpin peptides have antimicrobial potency with high selectivity and salt resistance.

    Science.gov (United States)

    Chou, Shuli; Shao, Changxuan; Wang, Jiajun; Shan, Anshan; Xu, Lin; Dong, Na; Li, Zhongyu

    2016-01-01

    The β-hairpin structure has been proposed to exhibit potent antimicrobial properties with low cytotoxicity, thus, multiple β-hairpin structures have been proved to be highly stable in structures containing tightly packed hydrophobic cores. The aim of this study was to develop peptide-based synthetic strategies for generating short, but effective AMPs as inexpensive antimicrobial agents. Multiple-stranded β-hairpin peptides with the same β-hairpin unit, (WRXxRW)n where n=1, 2, 3, or 4 and Xx represent the turn sequence, were synthesized, and their potential as antimicrobial agents was evaluated. Owning to the tightly packed hydrophobic core and paired Trp of this multiple-stranded β-hairpin structure, all the 12-residues peptides exhibited high cell selectivity towards bacterial cells over human red blood cells (hRBCs), and the peptide W2 exhibited stronger antimicrobial activities with the MIC values of 2-8μM against various tested bacteria. Not only that, but W2 also showed obvious synergy with streptomycin and chloramphenicol against Escherichia coli, and displayed synergy with ciprofloxacin against Staphylococcus aureus with the FICI values ⩽0.5. Fluorescence spectroscopy and electron microscopy analyses indicated that W2 kills microbial cells by permeabilizing the cell membrane and damaging membrane integrity. Collectively, based on the multiple β-hairpin peptides, the ability to develop libraries of short and effective peptides will be a powerful approach to the discovery of novel antimicrobial agents. We successfully screened a peptide W2 ((WRPGRW)2) from a series of multiple-stranded β-hairpin antimicrobial peptides based on the "S-shaped" motif that induced the formation of a globular structure, and Trp zipper was used to replace the disulfide bonds to reduce the cost of production. This novel structure applied to AMPs improved cell selectivity and salt stability. The findings of this study will promote the development of peptide

  6. Structural Insights into the Mechanisms of Action of Short-Peptide HIV-1 Fusion Inhibitors Targeting the Gp41 Pocket

    Directory of Open Access Journals (Sweden)

    Xiujuan Zhang

    2018-02-01

    Full Text Available The deep hydrophobic pocket of HIV-1 gp41 has been considered a drug target, but short-peptides targeting this site usually lack potent antiviral activity. By applying the M-T hook structure, we previously generated highly potent short-peptide fusion inhibitors that specifically targeted the pocket site, such as MT-SC22EK, HP23L, and LP-11. Here, the crystal structures of HP23L and LP-11 bound to the target mimic peptide N36 demonstrated the critical intrahelical and interhelical interactions, especially verifying that the hook-like conformation was finely adopted while the methionine residue was replaced by the oxidation-less prone residue leucine, and that addition of an extra glutamic acid significantly enhanced the binding and inhibitory activities. The structure of HP23L bound to N36 with two mutations (E49K and L57R revealed the critical residues and motifs mediating drug resistance and provided new insights into the mechanism of action of inhibitors. Therefore, the present data help our understanding for the structure-activity relationship (SAR of HIV-1 fusion inhibitors and facilitate the development of novel antiviral drugs.

  7. Molecular Self-Assembly of Short Aromatic Peptides: From Biology to Nanotechnology and Material Science

    Science.gov (United States)

    Gazit, Ehud

    2013-03-01

    The formation of ordered amyloid fibrils is the hallmark of several diseases of unrelated origin. In spite of grave clinical consequence, the mechanism of amyloid formation is not fully understood. We have suggested, based on experimental and bioinformatic analysis, that aromatic interactions may provide energetic contribution as well as order and directionality in the molecular-recognition and self-association processes that lead to the formation of these assemblies. This is in line with the well-known central role of aromatic-stacking interactions in self-assembly processes. Our works on the mechanism of aromatic peptide self-assembly, lead to the discovery that the diphenylalanine recognition motif self-assembles into peptide nanotubes with a remarkable persistence length. Other aromatic homodipeptides could self-assemble in nano-spheres, nano-plates, nano-fibrils and hydrogels with nano-scale order. We demonstrated that the peptide nanostructures have unique chemical, physical and mechanical properties including ultra-rigidity as aramides, semi-conductive, piezoelectric and non-linear optic properties. We also demonstrated the ability to use these peptide nanostructures as casting mold for the fabrication of metallic nano-wires and coaxial nano-cables. The application of the nanostructures was demonstrated in various fields including electrochemical biosensors, tissue engineering, and molecular imaging. Finally, we had developed ways for depositing of the peptide nanostructures and their organization. We had use inkjet technology as well as vapour deposition methods to coat surface and from the peptide ``nano-forests''. We recently demonstrated that even a single phenylalanine amino-acid can form well-ordered fibrilar assemblies.

  8. Glucagon-like peptide 2 improves nutrient absorption and nutritional status in short-bowel patients with no colon

    DEFF Research Database (Denmark)

    Jeppesen, P B; Hartmann, B; Thulesen, J

    2001-01-01

    Glucagon-like peptide 2 (GLP-2) is intestinotrophic, antisecretory, and transit-modulating in rodents, and it is mainly secreted from the intestinal mucosa of the terminal ileum and colon after food ingestion. We assessed the effect of GLP-2 on the gastrointestinal function in patients without a ...... a terminal ileum and colon who have functional short-bowel syndrome with severe malabsorption of wet weight (>1.5 kg/day) and energy (>2.3 MJ/day) and no postprandial secretion of GLP-2....

  9. Folding Topology of a Short Coiled-Coil Peptide Structure Templated by an Oligonucleotide Triplex

    DEFF Research Database (Denmark)

    Lou, Chenguang; Christensen, Niels Johan; Martos Maldonado, Manuel Cristo

    2017-01-01

    by oligonucleotide duplex and triplex formation. POC synthesis was achieved by copper-free alkyne-azide cycloaddition between three oligonucleotides and a 23-mer peptide, which by itself exhibited multiple oligomeric states in solution. The oligonucleotide domain was designed to furnish a stable parallel triplex...

  10. Rapid phylogenetic and functional classification of short genomic fragments with signature peptides

    Directory of Open Access Journals (Sweden)

    Berendzen Joel

    2012-08-01

    Full Text Available Abstract Background Classification is difficult for shotgun metagenomics data from environments such as soils, where the diversity of sequences is high and where reference sequences from close relatives may not exist. Approaches based on sequence-similarity scores must deal with the confounding effects that inheritance and functional pressures exert on the relation between scores and phylogenetic distance, while approaches based on sequence alignment and tree-building are typically limited to a small fraction of gene families. We describe an approach based on finding one or more exact matches between a read and a precomputed set of peptide 10-mers. Results At even the largest phylogenetic distances, thousands of 10-mer peptide exact matches can be found between pairs of bacterial genomes. Genes that share one or more peptide 10-mers typically have high reciprocal BLAST scores. Among a set of 403 representative bacterial genomes, some 20 million 10-mer peptides were found to be shared. We assign each of these peptides as a signature of a particular node in a phylogenetic reference tree based on the RNA polymerase genes. We classify the phylogeny of a genomic fragment (e.g., read at the most specific node on the reference tree that is consistent with the phylogeny of observed signature peptides it contains. Using both synthetic data from four newly-sequenced soil-bacterium genomes and ten real soil metagenomics data sets, we demonstrate a sensitivity and specificity comparable to that of the MEGAN metagenomics analysis package using BLASTX against the NR database. Phylogenetic and functional similarity metrics applied to real metagenomics data indicates a signal-to-noise ratio of approximately 400 for distinguishing among environments. Our method assigns ~6.6 Gbp/hr on a single CPU, compared with 25 kbp/hr for methods based on BLASTX against the NR database. Conclusions Classification by exact matching against a precomputed list of signature

  11. Implications of lipid monolayer charge characteristics on their selective interactions with a short antimicrobial peptide.

    Science.gov (United States)

    Ciumac, Daniela; Campbell, Richard A; Xu, Hai; Clifton, Luke A; Hughes, Arwel V; Webster, John R P; Lu, Jian R

    2017-02-01

    Many antimicrobial peptides (AMPs) target bacterial membranes and they kill bacteria by causing structural disruptions. One of the fundamental issues however lies in the selective responses of AMPs to different cell membranes as a lack of selectivity can elicit toxic side effects to mammalian host cells. A key difference between the outer surfaces of bacterial and mammalian cells is the charge characteristics. We report a careful study of the binding of one of the representative AMPs, with the general sequence G(IIKK) 4 I-NH 2 (G 4 ), to the spread lipid monolayers of DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine) and DPPG (1,2-dipalmitoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (sodium salt)) mimicking the charge difference between them, using the combined measurements from Langmuir trough, Brewster angle microscopy (BAM) and neutron reflection (NR). The difference in pressure rise upon peptide addition into the subphase clearly demonstrated the different interactions arising from different lipid charge features. Morphological changes from the BAM imaging confirmed the association of the peptide into the lipid monolayers, but there was little difference between them. However, NR studies revealed that the peptide bound 4 times more onto the DPPG monolayer than onto the DPPC monolayer. Importantly, whilst the peptide could only be associated with the head groups of DPPC it was well penetrated into the entire DPPG monolayer, showing that the electrostatic interaction strengthened the hydrophobic interaction and that the combined molecular interactive processes increased the power of G 4 in disrupting the charged membranes. The results are discussed in the context of general antibacterial actions as observed from other AMPs and membrane lytic actions. Copyright © 2016. Published by Elsevier B.V.

  12. Nanomaterials enhance osteogenic differentiation of human mesenchymal stem cells similar to a short peptide of BMP-7

    Science.gov (United States)

    Lock, Jaclyn; Liu, Huinan

    2011-01-01

    Background Nanomaterials have unique advantages in controlling stem cell function due to their biomimetic characteristics and special biological and mechanical properties. Controlling adhesion and differentiation of stem cells is critical for tissue regeneration. Methods This in vitro study investigated the effects of nano-hydroxyapatite, nano-hydroxyapatite-polylactide- co-glycolide (PLGA) composites, and a bone morphogenetic protein (BMP-7)- derived short peptide (DIF-7c) on osteogenic differentiation of human mesenchymal stem cells (MSC). The peptide was chemically functionalized onto nano-hydroxyapatite, incorporated into a nanophase hydroxyapatite-PLGA composite or PLGA control, or directly injected into culture media. Results Unlike the PLGA control, the nano-hydroxyapatite-PLGA composites promoted adhesion of human MSC. Importantly, nano-hydroxyapatite and nano-hydroxyapatite-PLGA composites promoted osteogenic differentiation of human MSCs, comparable with direct injection of the DIF-7c peptide into culture media. Conclusion Nano-hydroxyapatite and nano-hydroxyapatite-PLGA composites provide a promising alternative in directing the adhesion and differentiation of human MSC. These nanocomposites should be studied further to clarify their effects on MSC functions and bone remodeling in vivo, eventually translating to clinical applications. PMID:22114505

  13. Short Synthetic β-Sheet Antimicrobial Peptides for the Treatment of Multidrug-Resistant Pseudomonas aeruginosa Burn Wound Infections.

    Science.gov (United States)

    Zhong, Guansheng; Cheng, Junchi; Liang, Zhen Chang; Xu, Liang; Lou, Weiyang; Bao, Chang; Ong, Zhan Yuin; Dong, Huihui; Yang, Yi Yan; Fan, Weimin

    2017-04-01

    Pseudomonas aeruginosa is often implicated in burn wound infections; its inherent drug resistance often renders these infections extremely challenging to treat. This is further compounded by the problem of emerging drug resistance and the dearth of novel antimicrobial drug discovery in recent years. In the perennial search for effective antimicrobial compounds, the authors identify short synthetic β-sheet folding peptides, IRIKIRIK (IK8L), IRIkIrIK (IK8-2D), and irikirik (IK8D) as prime candidates owing to their high potency against Gram-negative bacteria. In this study, the peptides are first assayed against 20 clinically isolated multidrug-resistant P. aeruginosa strains in comparison with the conventional antibiotics imipenem and ceftazidime, and IK8L is demonstrated to be the most effective. IK8L also exhibits superior antibacterial killing kinetics compared to imipenem and ceftazidime. From transmission electron microscopy, confocal microscopy, and protein release analyses, IK8L shows membrane-lytic antimicrobial mechanism. Repeated use of IK8L does not induce drug resistance, while the bacteria develop resistance against the antibiotics after several times of treatment at sublethal doses. Analysis of mouse blood serum chemistry reveals that peptide does not induce systemic toxicity. The potential utility of IK8L in the in vivo treatment of P. aeruginosa-infected burn wounds is further demonstrated in a mouse model. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Genetically encoded short peptide tags for orthogonal protein labeling by Sfp and AcpS phosphopantetheinyl transferases.

    Science.gov (United States)

    Zhou, Zhe; Cironi, Pablo; Lin, Alison J; Xu, Yangqing; Hrvatin, Sinisa; Golan, David E; Silver, Pamela A; Walsh, Christopher T; Yin, Jun

    2007-05-22

    Short peptide tags S6 and A1, each 12 residues in length, were identified from a phage-displayed peptide library as efficient substrates for site-specific protein labeling catalyzed by Sfp and AcpS phosphopantetheinyl transferases (PPTases), respectively. S6 and A1 tags were selected for useful levels of orthogonality in reactivities with the PPTases: the catalytic efficiency, kcat/Km of Sfp-catalyzed S6 serine phosphopantetheinylation was 442-fold greater than that for AcpS. Conversely, the kcat/Km of AcpS-catalyzed A1 labeling was 30-fold higher than that for Sfp-catalyzed A1 labeling. S6 and A1 peptide tags can be fused to N- or C-termini of proteins for orthogonal labeling of target proteins in cell lysates or on live cell surfaces. The development of the orthogonal S6 and A1 tags represents a significant enhancement of PPTase-catalyzed protein labeling, allowing tandem or iterative covalent attachment of small molecules of diverse structures to the target proteins with high efficiency and specificity.

  15. Selection of Prebiotic Molecules in Amphiphilic Environments

    Directory of Open Access Journals (Sweden)

    Christian Mayer

    2017-01-01

    Full Text Available A basic problem in all postulated pathways of prebiotic chemistry is the low concentration which generally is expected for interesting reactants in fluid environments. Even though compounds, like nucleobases, sugars or peptides, principally may form spontaneously under environmental conditions, they will always be rapidly diluted in an aqueous environment. In addition, any such reaction leads to side products which often exceed the desired compound and generally hamper the first steps of a subsequent molecular evolution. Therefore, a mechanism of selection and accumulation of relevant prebiotic compounds seems to be crucial for molecular evolution. A very efficient environment for selection and accumulation can be found in the fluid continuum circulating in tectonic fault zones. Vesicles which form spontaneously at a depth of approximately 1 km present a selective trap for amphiphilic molecules, especially for peptides composed of hydrophilic and hydrophobic amino acids in a suitable sequence. The accumulation effect is shown in a numeric simulation on a simplified model. Further, possible mechanisms of a molecular evolution in vesicle membranes are discussed. Altogether, the proposed scenario can be seen as an ideal environment for constant, undisturbed molecular evolution in and on cell-like compartments.

  16. Synthetic amphibian peptides and short amino-acids derivatives against planktonic cells and mature biofilm of Providencia stuartii clinical strains.

    Science.gov (United States)

    Ostrowska, Kinga; Kamysz, Wojciech; Dawgul, Małgorzata; Różalski, Antoni

    2014-01-01

    Over the last decade, the growing number of multidrug resistant strains limits the use of many of the currently available chemotherapeutic agents. Furthermore, bacterial biofilm, due to its complex structure, constitutes an effective barrier to conventional antibiotics. The in vitro activities of naturally occurring peptide (Citropin 1.1), chemically engineered analogue (Pexiganan), newly-designed, short amino-acid derivatives (Pal-KK-NH2, Pal-KKK-NH2, Pal-RRR-NH2) and six clinically used antimicrobial agents (Gatifloxacin, Ampicilin, Cefotaxime, Ceftriaxone, Cefuroxime and Cefalexin) were investigated against planktonic cells and mature biofilm of multidrug-resistant Providencia stuartii strains, isolated from urological catheters. The MICs, MBCs values were determined by broth microdilution technique. Inhibition of biofilm formation by antimicrobial agents as well as biofilm susceptibility assay were tested using a surrogate model based on the Crystal Violet method. The antimicrobial activity of amino-acids derivatives and synthetic peptides was compared to that of clinically used antibiotics. For planktonic cells, MICs of peptides and antibiotics ranged between 1 and 256 μg/ml and 256 and ≥ 2048 μg/ml, respectively. The MBCs values of Pexiganan, Citropin 1.1 and amino-acids derivatives were between 16 and 256 μg/ml, 64 and 256 μg/ml and 16 and 512 μg/ml, respectively. For clinically used antibiotics the MBCs values were above 2048 μg/ml. All of the tested peptides and amino-acids derivatives, showed inhibitory activity against P. stuartii biofilm formation, in relation to their concentrations. Pexiganan and Citropin 1.1 in concentration range 32 and 256 μg/ml caused both strong and complete suppression of biofilm formation. None of the antibiotics caused complete inhibition of biofilm formation process. The biofilm susceptibility assay verified the extremely poor antibiofilm activity of conventional antibiotics compared to synthetic peptides. The

  17. Phage displayed short peptides against cells of Candida albicans demonstrate presence of species, morphology and region specific carbohydrate epitopes.

    Directory of Open Access Journals (Sweden)

    Soshee Anandakumar

    Full Text Available Candida albicans is a commensal opportunistic pathogen, which can cause superficial infections as well as systemic infections in immuocompromised hosts. Among nosocomial fungal infections, infections by C. albicans are associated with highest mortality rates even though incidence of infections by other related species is on the rise world over. Since C. albicans and other Candida species differ in their susceptibility to antifungal drug treatment, it is crucial to accurately identify the species for effective drug treatment. Most diagnostic tests that differentiate between C. albicans and other Candida species are time consuming, as they necessarily involve laboratory culturing. Others, which employ highly sensitive PCR based technologies often, yield false positives which is equally dangerous since that leads to unnecessary antifungal treatment. This is the first report of phage display technology based identification of short peptide sequences that can distinguish C. albicans from other closely related species. The peptides also show high degree of specificity towards its different morphological forms. Using fluorescence microscopy, we show that the peptides bind on the surface of these cells and obtained clones that could even specifically bind to only specific regions of cells indicating restricted distribution of the epitopes. What was peculiar and interesting was that the epitopes were carbohydrate in nature. This gives insight into the complexity of the carbohydrate composition of fungal cell walls. In an ELISA format these peptides allow specific detection of relatively small numbers of C. albicans cells. Hence, if used in combination, such a test could help accurate diagnosis and allow physicians to initiate appropriate drug therapy on time.

  18. Next-generation ELISA diagnostic assay for Chagas Disease based on the combination of short peptidic epitopes

    Science.gov (United States)

    Volcovich, Romina; Altcheh, Jaime; Bracamonte, Estefanía; Marco, Jorge D.; Nielsen, Morten; Buscaglia, Carlos A.

    2017-01-01

    Chagas Disease, caused by the protozoan Trypanosoma cruzi, is a major health and economic problem in Latin America for which no vaccine or appropriate drugs for large-scale public health interventions are yet available. Accurate diagnosis is essential for the early identification and follow up of vector-borne cases and to prevent transmission of the disease by way of blood transfusions and organ transplantation. Diagnosis is routinely performed using serological methods, some of which require the production of parasite lysates, parasite antigenic fractions or purified recombinant antigens. Although available serological tests give satisfactory results, the production of reliable reagents remains laborious and expensive. Short peptides spanning linear B-cell epitopes have proven ideal serodiagnostic reagents in a wide range of diseases. Recently, we have conducted a large-scale screening of T. cruzi linear B-cell epitopes using high-density peptide chips, leading to the identification of several hundred novel sequence signatures associated to chronic Chagas Disease. Here, we performed a serological assessment of 27 selected epitopes and of their use in a novel multipeptide-based diagnostic method. A combination of 7 of these peptides were finally evaluated in ELISA format against a panel of 199 sera samples (Chagas-positive and negative, including sera from Leishmaniasis-positive subjects). The multipeptide formulation displayed a high diagnostic performance, with a sensitivity of 96.3% and a specificity of 99.15%. Therefore, the use of synthetic peptides as diagnostic tools are an attractive alternative in Chagas’ disease diagnosis. PMID:28991925

  19. Next-generation ELISA diagnostic assay for Chagas Disease based on the combination of short peptidic epitopes.

    Directory of Open Access Journals (Sweden)

    Juan Mucci

    2017-10-01

    Full Text Available Chagas Disease, caused by the protozoan Trypanosoma cruzi, is a major health and economic problem in Latin America for which no vaccine or appropriate drugs for large-scale public health interventions are yet available. Accurate diagnosis is essential for the early identification and follow up of vector-borne cases and to prevent transmission of the disease by way of blood transfusions and organ transplantation. Diagnosis is routinely performed using serological methods, some of which require the production of parasite lysates, parasite antigenic fractions or purified recombinant antigens. Although available serological tests give satisfactory results, the production of reliable reagents remains laborious and expensive. Short peptides spanning linear B-cell epitopes have proven ideal serodiagnostic reagents in a wide range of diseases. Recently, we have conducted a large-scale screening of T. cruzi linear B-cell epitopes using high-density peptide chips, leading to the identification of several hundred novel sequence signatures associated to chronic Chagas Disease. Here, we performed a serological assessment of 27 selected epitopes and of their use in a novel multipeptide-based diagnostic method. A combination of 7 of these peptides were finally evaluated in ELISA format against a panel of 199 sera samples (Chagas-positive and negative, including sera from Leishmaniasis-positive subjects. The multipeptide formulation displayed a high diagnostic performance, with a sensitivity of 96.3% and a specificity of 99.15%. Therefore, the use of synthetic peptides as diagnostic tools are an attractive alternative in Chagas' disease diagnosis.

  20. How proteases from Enterococcus faecalis contribute to its resistance to short alpha-helical antimicrobial peptides

    Czech Academy of Sciences Publication Activity Database

    Nešuta, Ondřej; Buděšínský, Miloš; Hadravová, Romana; Monincová, Lenka; Humpolíčková, Jana; Čeřovský, Václav

    2017-01-01

    Roč. 75, č. 7 (2017), č. článku ftx091. ISSN 2049-632X R&D Projects: GA TA ČR(CZ) TA04010638; GA MZd(CZ) NV16-27726A Institutional support: RVO:61388963 Keywords : antimicrobial peptides * biofilm * C-terminal deamidation * gelatinase * protease Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 2.335, year: 2016

  1. Functional importance of short-range binding and long-range solvent interactions in helical antifreeze peptides.

    Science.gov (United States)

    Ebbinghaus, Simon; Meister, Konrad; Prigozhin, Maxim B; Devries, Arthur L; Havenith, Martina; Dzubiella, Joachim; Gruebele, Martin

    2012-07-18

    Short-range ice binding and long-range solvent perturbation both have been implicated in the activity of antifreeze proteins and antifreeze glycoproteins. We study these two mechanisms for activity of winter flounder antifreeze peptide. Four mutants are characterized by freezing point hysteresis (activity), circular dichroism (secondary structure), Förster resonance energy transfer (end-to-end rigidity), molecular dynamics simulation (structure), and terahertz spectroscopy (long-range solvent perturbation). Our results show that the short-range model is sufficient to explain the activity of our mutants, but the long-range model provides a necessary condition for activity: the most active peptides in our data set all have an extended dynamical hydration shell. It appears that antifreeze proteins and antifreeze glycoproteins have reached different evolutionary solutions to the antifreeze problem, utilizing either a few precisely positioned OH groups or a large quantity of OH groups for ice binding, assisted by long-range solvent perturbation. Copyright © 2012 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  2. Solvent polarity controls the helical conformation of short peptides rich in Calpha-tetrasubstituted amino acids.

    Science.gov (United States)

    Bellanda, Massimo; Mammi, Stefano; Geremia, Silvano; Demitri, Nicola; Randaccio, Lucio; Broxterman, Quirinus B; Kaptein, Bernard; Pengo, Paolo; Pasquato, Lucia; Scrimin, Paolo

    2007-01-01

    The two peptides, rich in C(alpha)-tetrasubstituted amino acids, Ac-[Aib-L-(alphaMe)Val-Aib](2)-L-His-NH(2) (1) and Ac-[Aib-L-(alphaMe)Val-Aib](2)-O-tBu (2 a) are prevalently helical. They present the unique property of changing their conformation from the alpha- to the 3(10)-helix as a function of the polarity of the solvent: alpha in more polar solvents, 3(10) in less polar ones. Conclusive evidence of this reversible change of conformation is reported on the basis of the circular dichroism (CD) spectra and a detailed two-dimensional NMR analysis in two solvents (trifluoroethanol and methanol) refined with molecular dynamics calculations. The X-ray diffractometric analysis of the crystals of both peptides reveals that they assume a prevalent 3(10)-helix conformation in the solid state. This conformation is practically superimposable on that obtained from the NMR analysis of 1 in methanol. The NMR results further validate the reported CD signature of the 3(10)-helix and the use of the CD technique for its assessment.

  3. Concatemerization increases the inhibitory activity of short, cell-penetrating, cationic and tryptophan-rich antifungal peptides.

    Science.gov (United States)

    López-García, Belén; Harries, Eleonora; Carmona, Lourdes; Campos-Soriano, Lidia; López, José Javier; Manzanares, Paloma; Gandía, Mónica; Coca, María; Marcos, Jose F

    2015-10-01

    There are short cationic and tryptophan-rich antifungal peptides such as the hexapeptide PAF26 (RKKWFW) that have selective toxicity and cell penetration properties against fungal cells. This study demonstrates that concatemeric peptides with tandem repeats of the heptapeptide PAF54 (which is an elongated PAF26 sequence) show increased fungistatic and bacteriostatic activities while maintaining the absence of hemolytic activity of the monomer. The increase in antimicrobial activity of the double-repeated PAF sequences (diPAFs), compared to the nonrepeated PAF, was higher (4-8-fold) than that seen for the triple-repeated sequences (triPAFs) versus the diPAFs (2-fold). However, concatemerization diminished the fungicidal activity against quiescent spores of the filamentous fungus Penicillium digitatum. Peptide solubility and sensitivity to proteolytic degradation were affected by the design of the concatemers: incorporation of the AGPA sequence hinge to separate PAF54 repeats increased solubility while the C-terminal addition of the KDEL sequence decreased in vitro stability. These results led to the design of the triPAF sequence PAF102 of 30 amino acid residues, with increased antimicrobial activity and minimal inhibitory concentration (MIC) value of 1-5 μM depending on the fungus. Further characterization of the mode-of-action of PAF102 demonstrated that it colocalizes first with the fungal cell wall, it is thereafter internalized in an energy dependent manner into hyphal cells of the filamentous fungus Fusarium proliferatum, and finally kills hyphal cells intracellularly. Therefore, PAF102 showed mechanistic properties against fungi similar to the parental PAF26. These observations are of high interest in the future development of PAF-based antimicrobial molecules optimized for their production in biofactories.

  4. Synergistic effect of supplemental enteral nutrients and exogenous glucagon-like peptide 2 on intestinal adaptation in a rat model of short bowel syndrome

    DEFF Research Database (Denmark)

    Liu, Xiaowen; Nelson, David W; Holst, Jens Juul

    2006-01-01

    BACKGROUND: Short bowel syndrome (SBS) can lead to intestinal failure and require total or supplemental parenteral nutrition (TPN or PN, respectively). Glucagon-like peptide 2 (GLP-2) is a nutrient-dependent, proglucagon-derived gut hormone that stimulates intestinal adaptation. OBJECTIVE: Our...... of GLP-2 (SEN x GLP-2 interaction, P cellularity and digestive capacity in parenterally fed rats with SBS...

  5. N-terminal diproline and charge group effects on the stabilization of helical conformation in alanine-based short peptides: CD studies with water and methanol as solvent.

    Science.gov (United States)

    Goyal, Bhupesh; Srivastava, Kinshuk Raj; Durani, Susheel

    2017-06-01

    Protein folding problem remains a formidable challenge as main chain, side chain and solvent interactions remain entangled and have been difficult to resolve. Alanine-based short peptides are promising models to dissect protein folding initiation and propagation structurally as well as energetically. The effect of N-terminal diproline and charged side chains is assessed on the stabilization of helical conformation in alanine-based short peptides using circular dichroism (CD) with water and methanol as solvent. A1 (Ac-Pro-Pro-Ala-Lys-Ala-Lys-Ala-Lys-Ala-NH 2 ) is designed to assess the effect of N-terminal homochiral diproline and lysine side chains to induce helical conformation. A2 (Ac-Pro-Pro-Glu-Glu-Ala-Ala-Lys-Lys-Ala-NH 2 ) and A3 (Ac-dPro-Pro-Glu-Glu-Ala-Ala-Lys-Lys-Ala-NH 2 ) with N-terminal homochiral and heterochiral diproline, respectively, are designed to assess the effect of Glu...Lys (i, i + 4) salt bridge interactions on the stabilization of helical conformation. The CD spectra of A1, A2 and A3 in water manifest different amplitudes of the observed polyproline II (PPII) signals, which indicate different conformational distributions of the polypeptide structure. The strong effect of solvent substitution from water to methanol is observed for the peptides, and CD spectra in methanol evidence A2 and A3 as helical folds. Temperature-dependent CD spectra of A1 and A2 in water depict an isodichroic point reflecting coexistence of two conformations, PPII and β-strand conformation, which is consistent with the previous studies. The results illuminate the effect of N-terminal diproline and charged side chains in dictating the preferences for extended-β, semi-extended PPII and helical conformation in alanine-based short peptides. The results of the present study will enhance our understanding on stabilization of helical conformation in short peptides and hence aid in the design of novel peptides with helical structures. Copyright © 2017 European Peptide

  6. A Short Synthetic Peptide Mimetic of Apolipoprotein A1 Mediates Cholesterol and Globotriaosylceramide Efflux from Fabry Fibroblasts.

    Science.gov (United States)

    Schueler, Ulrike; Kaneski, Christine; Remaley, Alan; Demosky, Stephen; Dwyer, Nancy; Blanchette-Mackie, Joan; Hanover, John; Brady, Roscoe

    2016-01-01

    Fabry disease is an X-linked sphingolipid storage disorder caused by a deficiency of the lysosomal enzyme α-galactosidase A (AGA, EC 3.2.1.22) resulting in the intracellular accumulation of globotriaosylceramide (Gb3). We found that Gb3 storage also correlates with accumulation of endosomal-lysosomal cholesterol in Fabry fibroblasts. This cholesterol accumulation may contribute to the phenotypic pathology of Fabry disease by slowing endosomal-lysosomal trafficking. We found that LDL receptor expression is not downregulated in Fabry fibroblasts resulting in accumulation of both cholesterol and Gb3. 5A-Palmitoyl oleoyl-phosphatidylcholine (5AP) is a phospholipid complex containing a short synthetic peptide that mimics apolipoprotein A1, the main protein component of high-density lipoprotein (HDL) that mediates the efflux of cholesterol from cells via the ATP-binding cassette transporter. We used 5AP and HDL to remove cholesterol from Fabry fibroblasts to examine the fate of accumulated cellular Gb3. Using immunostaining techniques, we found that 5AP is highly effective for depleting cholesterol and Gb3 in these cells. 5AP restores the ApoA-1-mediated cholesterol efflux leading to mobilization of cholesterol and reduction of Gb3 in Fabry fibroblasts.

  7. Short (

    NARCIS (Netherlands)

    Telleman, Gerdien; den Hartog, Laurens

    2013-01-01

    Aim: This systematic review assessed the implant survival rate of short (<10 mm) dental implants installed in partially edentulous patients. A case report of a short implant in the posterior region have been added. Materials and methods: A search was conducted in the electronic databases of MEDLINE

  8. Modulating the activity of short arginine-tryptophan containing antibacterial peptides with N-terminal metallocenoyl groups

    Directory of Open Access Journals (Sweden)

    H. Bauke Albada

    2012-10-01

    Full Text Available A series of small synthetic arginine and tryptophan containing peptides was prepared and analyzed for their antibacterial activity. The effect of N-terminal substitution with metallocenoyl groups such as ferrocene (FcCO and ruthenocene (RcCO was investigated. Antibacterial activity in different media, growth inhibition, and killing kinetics of the most active peptides were determined. The toxicity of selected derivatives was determined against erythrocytes and three human cancer cell lines. It was shown that the replacement of an N-terminal arginine residue with a metallocenoyl moiety modulates the activity of WRWRW-peptides against Gram-positive and Gram-negative bacteria. MIC values of 2–6 µM for RcCO-W(RW2 and 1–11 µM for (RW3 were determined. Interestingly, W(RW2-peptides derivatized with ferrocene were significantly less active than those derivatized with ruthenocene which have similar structural but different electronic properties, suggesting a major influence of the latter. The high activities observed for the RcCO-W(RW2- and (RW3-peptides led to an investigation of the origin of activity of these peptides using several important activity-related parameters. Firstly, killing kinetics of the RcCO-W(RW2-peptide versus killing kinetics of the (RW3 derivative showed faster reduction of the colony forming units for the RcCO-W(RW2-peptide, although MIC values indicated higher activity for the (RW3-peptide. This was confirmed by growth inhibition studies. Secondly, hemolysis studies revealed that both peptides did not lead to significant destruction of erythrocytes, even up to 500 µg/mL for (RW3 and 250 µg/mL for RcCO-W(RW2. In addition, toxicity against three human cancer cell lines (HepG2, HT29, MCF7 showed that the (RW3-peptide had an IC50 value of ~140 µM and the RcW(RW2 one of ~90 µM, indicating a potentially interesting therapeutic window. Both the killing kinetics and growth inhibition studies presented in this work point to a

  9. Self-assembly of short peptides composed of only aliphatic amino acids and a combination of aromatic and aliphatic amino acids.

    Science.gov (United States)

    Subbalakshmi, Chilukuri; Manorama, Sunkara V; Nagaraj, Ramakrishnan

    2012-05-01

    The morphology of structures formed by the self-assembly of short N-terminal t-butyloxycarbonyl (Boc) and C-terminal methyl ester (OMe) protected and Boc-deprotected hydrophobic peptide esters was investigated. We have observed that Boc-protected peptide esters composed of either only aliphatic hydrophobic amino acids or aliphatic hydrophobic amino acids in combination with aromatic amino acids, formed highly organized structures, when dried from methanol solutions. Transmission and scanning electron microscopic images of the peptides Boc-Ile-Ile-OMe, Boc-Phe-Phe-Phe-Ile-Ile-OMe and Boc-Trp-Ile-Ile-OMe showed nanotubular structures. Removal of the Boc group resulted in disruption of the ability to form tubular structures though spherical aggregates were formed. Both Boc-Leu-Ile-Ile-OMe and H-Leu-Ile-Ile-OMe formed only spherical nanostructures. Dynamic light scattering studies showed that aggregates of varying dimensions were present in solution suggesting that self-assembly into ordered structures is facilitated by aggregation in solution. Fourier transform infrared spectroscopy and circular dichroism spectroscopy data show that although all four of the protected peptides adopt well-defined tertiary structures, upon removal of the Boc group, only H-Phe-Phe-Phe-Ile-Ile-OMe had the ability to adopt β-structure. Our results indicate that hydrophobic interaction is a very important determinant for self-assembly and presence of charged and aromatic amino acids in a peptide is not necessary for self-assembly. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.

  10. Structural insights into Cn-AMP1, a short disulfide-free multifunctional peptide from green coconut water.

    Science.gov (United States)

    Santana, Mábio J; de Oliveira, Aline L; Queiroz Júnior, Luiz H K; Mandal, Santi M; Matos, Carolina O; Dias, Renata de O; Franco, Octavio L; Lião, Luciano M

    2015-02-27

    Multifunctional and promiscuous antimicrobial peptides (AMPs) can be used as an efficient strategy to control pathogens. However, little is known about the structural properties of plant promiscuous AMPs without disulfide bonds. CD and NMR were used to elucidate the structure of the promiscuous peptide Cn-AMP1, a disulfide-free peptide isolated from green coconut water. Data here reported shows that peptide structure is transitory and could be different according to the micro-environment. In this regard, Cn-AMP1 showed a random coil in a water environment and an α-helical structure in the presence of SDS-d25 micelles. Moreover, deuterium exchange experiments showed that Gly4, Arg5 and Met9 residues are less accessible to solvent, suggesting that flexibility and cationic charges seem to be essential for Cn-AMP1 multiple activities. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  11. Tailorable Exciton Transport in Doped Peptide–Amphiphile Assemblies

    Energy Technology Data Exchange (ETDEWEB)

    Solomon, Lee A. [Center; Sykes, Matthew E. [Center; Wu, Yimin A. [Center; Schaller, Richard D. [Center; Department; Wiederrecht, Gary P. [Center; Fry, H. Christopher [Center

    2017-08-29

    Light-harvesting biomaterials are an attractive target in photovoltaics, photocatalysis, and artificial photosynthesis. Through peptide self-assembly, complex nanostructures can be engineered to study the role of chromophore organization during light absorption and energy transport. To this end, we demonstrate the one-dimensional transport of excitons along naturally occurring, light-harvesting, Zn-protoporphyrin IX chromophores within self-assembled peptide-amphiphile nanofibers. The internal structure of the nanofibers induces packing of the porphyrins into linear chains. We find that this peptide assembly can enable long-range exciton diffusion, yet it also induces the formation of excimers between adjacent molecules, which serve as exciton traps. Electronic coupling between neighboring porphyrin molecules is confirmed by various spectroscopic methods. The exciton diffusion process is then probed through transient photoluminescence and absorption measurements and fit to a model for one-dimensional hopping. Because excimer formation impedes exciton hopping, increasing the interchromophore spacing allows for improved diffusivity, which we control through porphyrin doping levels. We show that diffusion lengths of over 60 nm are possible at low porphyrin doping, representing an order of magnitude improvement over the highest doping fractions.

  12. Effect of Asp 96 isomerization on the properties of a lens αB-crystallin-derived short peptide.

    Science.gov (United States)

    Takata, Takumi; Fujii, Noriko

    2015-12-10

    One of the major reasons for age-related cataract formation is an accumulation of insoluble lens proteins. In particular, higher-order α-crystallin aggregates, comprising αA and αB subunits, are insolubilized by the build up of various post-translational modifications over time. Although we previously found an exceptional amount of Asp96 isomerization in αB-crystallin from aged human lens, the biological effect remains unknown. To approximate the effect of Asp 96 isomerization in αB-crystallin, here residues 93-103 of αB-crystallin were chemically synthesized as peptides in which l-α-Asp was replaced with l-β-Asp, D-α-Asp, or D-β-Asp. The resulting peptides were then compared in a biological assay. The results showed that isomerization of Asp 96 altered both the local structure of peptide and its stability against enzymatic digestion. In addition, the synthesized peptides decreased the insoluble fraction of heated α-crystallin. The D-β-Asp-containing peptide further decreased heat-induced precipitation of α-crystallin, and a chaperone assay based on heated alcohol dehydrogenase implied differential interaction of the peptides with substrate depending on the Asp isomer present in each. Our results suggest that the formation of Asp isomers is likely to affect the higher-order oligomer structure of α-crystallin and thereby its chaperone functions in aged lens. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Immunomodulatory activity of chicken NK-lysin peptides

    Science.gov (United States)

    Chicken NK-lysin (cNK-lysin), the chicken homologue of human granulysin, is a cationic amphiphilic antimicrobial peptide (AMP) produced by cytotoxic T cells and natural killer cells. We have previously demonstrated that cNK-lysin and cNK-2, which is a synthetic peptide incorporating core alpha-helic...

  14. Lattice Models of Amphiphile and Solvent Mixtures.

    Science.gov (United States)

    Brindle, David

    Available from UMI in association with The British Library. Materials based on amphiphilic molecules have a wide range of industrial applications and are of fundamental importance in the structure of many biological systems. Their importance derives from their behaviour as surface-active agents in solubilization applications and because of their ability to form systems with varying degrees of structural order such as micelles, bilayers and liquid crystal phases. The nature of the molecular ordering is of importance both during the processing of these materials and in their final application. A Monte Carlo simulation of a three dimensional lattice model of an amphiphile and solvent mixture has been developed as an extension of earlier work in two dimensions. In the earlier investigation the simulation was carried out with three segment amphiphiles on a two dimensional lattice and cluster size distributions were determined for a range of temperatures, amphiphile concentrations and intermolecular interaction energies. In the current work, a wider range of structures are observed including micelles, bilayers and a vesicle. The structures are studied as a function of temperature, chain length, amphiphile concentration and intermolecular interaction energies. Clusters are characterised according to their shape, size and surface roughness. A detailed temperature -concentration phase diagram is presented for a system with four segment amphiphiles. The phase diagram shows a critical micelle concentration (c.m.c.) at low amphiphile concentrations and a transition from a bicontinuous to lamellar region at amphiphile concentrations around 50%. At high amphiphile concentrations, there is some evidence for the formation of a gel. The results obtained question the validity of current models of the c.m.c. The Monte Carlo simulations require extensive computing power and the simulation was carried out on a transputer array, where the parallel architecture allows high speed. The

  15. Spider Neurotoxins, Short Linear Cationic Peptides and Venom Protein Classification Improved by an Automated Competition between Exhaustive Profile HMM Classifiers.

    Science.gov (United States)

    Koua, Dominique; Kuhn-Nentwig, Lucia

    2017-08-08

    Spider venoms are rich cocktails of bioactive peptides, proteins, and enzymes that are being intensively investigated over the years. In order to provide a better comprehension of that richness, we propose a three-level family classification system for spider venom components. This classification is supported by an exhaustive set of 219 new profile hidden Markov models (HMMs) able to attribute a given peptide to its precise peptide type, family, and group. The proposed classification has the advantages of being totally independent from variable spider taxonomic names and can easily evolve. In addition to the new classifiers, we introduce and demonstrate the efficiency of hmmcompete , a new standalone tool that monitors HMM-based family classification and, after post-processing the result, reports the best classifier when multiple models produce significant scores towards given peptide queries. The combined used of hmmcompete and the new spider venom component-specific classifiers demonstrated 96% sensitivity to properly classify all known spider toxins from the UniProtKB database. These tools are timely regarding the important classification needs caused by the increasing number of peptides and proteins generated by transcriptomic projects.

  16. Peptide nanocarriers for intracellular delivery of photosensitizers

    NARCIS (Netherlands)

    Hell, A.J. van; Fretz, M.M.; Crommelin, D.J.A.; Hennink, W.E.; Mastrobattista, E.

    Previously we have shown that recombinantly produced amphiphilic oligopeptides with amino acid sequence Ac-Ala-Ala-Val-Val-Leu-Leu-Leu-Trp-Glu-Glu spontaneously assemble into nano-sized vesicles with an average diameter of 120 nm. Moreover, peptide vesicles could be stabilized by introducing

  17. Synergistic effect of supplemental enteral nutrients and exogenous glucagon-like peptide 2 on intestinal adaptation in a rat model of short bowel syndrome

    DEFF Research Database (Denmark)

    Liu, Xiaowen; Nelson, David W; Holst, Jens Juul

    2006-01-01

    BACKGROUND: Short bowel syndrome (SBS) can lead to intestinal failure and require total or supplemental parenteral nutrition (TPN or PN, respectively). Glucagon-like peptide 2 (GLP-2) is a nutrient-dependent, proglucagon-derived gut hormone that stimulates intestinal adaptation. OBJECTIVE: Our...... objective was to determine whether supplemental enteral nutrients (SEN) modulate the intestinotrophic response to a low dose of GLP-2 coinfused with PN in a rat model of SBS (60% jejunoileal resection plus cecectomy). DESIGN: Rats were randomly assigned to 8 treatments by using a 2 x 2 x 2 factorial design...

  18. Glucagon-like peptide 2 improves nutrient absorption and nutritional status in short-bowel patients with no colon

    DEFF Research Database (Denmark)

    Jeppesen, P B; Hartmann, B; Thulesen, J

    2001-01-01

    Glucagon-like peptide 2 (GLP-2) is intestinotrophic, antisecretory, and transit-modulating in rodents, and it is mainly secreted from the intestinal mucosa of the terminal ileum and colon after food ingestion. We assessed the effect of GLP-2 on the gastrointestinal function in patients without...

  19. Next-generation ELISA diagnostic assay for Chagas Disease based on the combination of short peptidic epitopes

    DEFF Research Database (Denmark)

    Mucci, Juan; Carmona, Santiago J.; Volcovich, Romina

    2017-01-01

    method. A combination of 7 of these peptides were finally evaluated in ELISA format against a panel of 199 sera samples (Chagas-positive and negative, including sera from Leishmaniasis-positive subjects). The multipeptide formulation displayed a high diagnostic performance, with a sensitivity of 96...

  20. Search for Fibrous Aggregates Potentially Useful in Regenerative Medicine Formed under Physiological Conditions by Self-Assembling Short Peptides Containing Two Identical Aromatic Amino Acid Residues

    Directory of Open Access Journals (Sweden)

    Justyna Fraczyk

    2018-03-01

    Full Text Available This study investigates the propensity of short peptides to self-organize and the influence of aggregates on cell cultures. The dipeptides were derived from both enantiomers of identical aromatic amino acids and tripeptides were prepared from two identical aromatic amino acids with one cysteine or methionine residue in the C-terminal, N-terminal, or central position. The formation or absence of fibrous structures under physiological conditions was established using Congo Red and Thioflavine T assays as well as by microscopic examination using normal and polarized light. The in vitro stability of the aggregates in buffered saline solution was assessed over 30 days. Materials with potential for use in regenerative medicine were selected based on the cytotoxicity of the peptides to the endothelial cell line EA.hy 926 and the wettability of the surfaces of the films, as well as using scanning electron microscopy. The criteria were fulfilled by H-dPhedPhe-OH, H-dCysdPhedPhe-OH, H-CysTyrTyr-OH, H-dPhedPhedCys-OH, H-TyrTyrMet-OH, and H–TyrMetTyr–OH. Our preliminary results suggest that the morphology and cell viability of L919 fibroblast cells do not depend on the stereochemistry of the self-organizing peptides.

  1. Short bowel patients treated for two years with glucagon-like Peptide 2: effects on intestinal morphology and absorption, renal function, bone and body composition, and muscle function

    DEFF Research Database (Denmark)

    Jeppesen, P B; Lund, P; Gottschalck, I B

    2009-01-01

    demonstrated in energy intake or absorption, and GLP-2 did not significantly affect mucosal morphology, body composition, bone mineral density or muscle function. CONCLUSIONS: GLP-2 treatment reduces fecal weight by approximately 1000 g/d and enables SBS patients to maintain their intestinal fluid......BACKGROUND AND AIMS: In a short-term study, Glucagon-like peptide 2 (GLP-2) has been shown to improve intestinal absorption in short bowel syndrome (SBS) patients. This study describes longitudinal changes in relation to GLP-2 treatment for two years. METHODS: GLP-2, 400 micrograms, s.c.,TID, were...... and bone mineral density (by DEXA), biochemical markers of bone turnover (by s-CTX and osteocalcin, PTH and vitamin D), and muscle function (NMR, lungfunction, exercise test) were measured. RESULTS: GLP-2 compliance was >93%. Three of eleven patients did not complete the study. In the remaining 8 patients...

  2. An Amylase-Responsive Bolaform Supra-Amphiphile.

    Science.gov (United States)

    Kang, Yuetong; Cai, Zhengguo; Tang, Xiaoyan; Liu, Kai; Wang, Guangtong; Zhang, Xi

    2016-02-01

    An amylase-responsive bolaform supra-amphiphile was constructed by the complexation between β-cyclodextrin and a bolaform covalent amphiphile on the basis of host-guest interaction. The bolaform covalent amphiphile could self-assemble in solution, forming sheet-like aggregates and displaying weak fluorescence because of aggregation-induced quenching. The addition of β-cyclodextrin led to the formation of the bolaform supra-amphiphile, prohibiting the aggregation of the bolaform covalent amphiphile and accompanying with the significant recovery of fluorescence. Upon the addition of α-amylase, with the degradation β-cyclodextrin, the fluorescence of the supra-amphiphile would quench gradually and significantly, and the quenching rate linearly correlated to the concentration of α-amylase. This study enriches the field of supra-amphiphiles on the basis of noncovalent interactions, and moreover, it may provide a facile way to estimate the activity of α-amylase.

  3. Bola-amphiphile self-assembly

    DEFF Research Database (Denmark)

    Svaneborg, Carsten

    2012-01-01

    Bola-amphiphiles are rod-like molecules where both ends of the molecule likes contact with water, while the central part of the molecule dislikes contact with water. What do such molecules do when they are dissolved in water? They self-assemble into micelles. This is a Dissipartive particle...

  4. Fluctuations and structure of amphiphilic films

    International Nuclear Information System (INIS)

    Gourier, CH.

    1996-01-01

    This thesis is divided in three parts.The first part exposes in a theoretical point of view, how the fluctuations spectrum of an amphiphilic film is governed by its properties and its bidimensional characteristics.The measurements of fluctuations spectra of an interface are accessible with the measurement of intensity that interface diffuses out of the specular angle, we present in the second chapter the principles of the X rays diffusion by a real interface and see how the diffuse diffusion experiments allow to determine the fluctuations spectrum of an amphiphilic film. The second part is devoted to the different experimental techniques that have allowed to realize the study of fluctuation as well as the structural study.The third part is devoted to experimental results concerning the measurements of fluctuations spectra and to the study of the structure of amphiphilic films. We show that it is possible by using an intense source of X rays (ESRF: European Synchrotron Radiation Facility) to measure the water and amphiphilic films fluctuations spectra until molecular scales. The last chapter is devoted to the structural study and film fluctuations made of di-acetylenic molecules. (N.C.)

  5. Amphiphilic copolymers for fouling-release coatings

    DEFF Research Database (Denmark)

    Noguer, Albert Camós; Olsen, Stefan Møller; Hvilsted, Søren

    of the coatings [9,10,11]. This work shows the effect of an amphiphilic copolymer that induces hydrophilicity on the surface of the silicone-based fouling release coatings. The behaviour of these copolymers within the coating upon immersion and the interaction of these surface-active additives with other...

  6. Short synthetic peptides derived from viral proteins compete with HIV gp120 for the binding to CD4 receptors.

    Science.gov (United States)

    Chersi, A; Pugliese, O; Federico, A; Viora, M

    2000-01-01

    In the complex mechanism of adhesion, internalization, and infection of cells by human immunodeficiency virus (HIV) viral particles, a determinant role is played by the viral envelope glycoprotein gp120, which binds to CD4 receptors of T cells and monocytes. We tested the ability of a panel of 7- to 12-residue synthetic peptides, selected from the region 414-434 of the HIV-1 gp120, to inhibit the binding of the viral protein to CD4 receptors of cultured human lymphoid cells. The assay was based on the observation that the binding of gp120 to the receptors interferes with the binding of a specific anti-CD4 monoclonal antibody, as a result of the masking of the antibody epitope; thus, we tested whether preincubation of cells with the peptides before gp120 addition might restore the recognition of the CD4 molecule by the antibody. High expression of CD4 receptors was thus assumed as indication that the binding of the viral protein had been inhibited. Maximum activity was displayed by a 9-residue peptide located near the amino terminal end of the 414-434 fragment. In addition, several fragments deduced from other viral proteins, possessing partial amino acid sequence homology with the HIV gp120 fragment, exhibited a similar type of interaction with the CD4 receptor. All active peptides contain the Cys residue (position 423 of gp120). This residue is essential, although not sufficient, for inhibiting gp120 binding, as few other amino acid residues within the fragment play a complementary role in increasing or decreasing the inhibitory ability.

  7. Short sleep duration is associated with B-type natriuretic peptide levels and predicts the death of Japanese patients with type 2 diabetes.

    Science.gov (United States)

    Hamasaki, Hidetaka; Katsuyama, Hisayuki; Sako, Akahito; Yanai, Hidekatsu

    2017-08-01

    To investigate the associations of sleep duration with all-cause mortality, glycemic control, and other clinical parameters of patients with type 2 diabetes. From April 2013 to December 2015, we conducted a retrospective cohort study. Study participants were divided into three groups according to their sleep duration. Multiple regression analysis and Cox proportional hazards analysis were performed to assess the independent associations of sleep duration with clinical parameters and all-cause mortality. We enrolled 1233 patients who were then followed for 860 ± 264 days. During the follow-up period, 20 patients (1.6%) died. Sleep duration inversely associated with plasma B-type natriuretic peptide levels (β = -0.203, p = 0.012) in short (<7 h) sleepers, whereas it was positively associated with hemoglobin A1c levels (β = 0.156, p = 0.021) in long (≥9 h) sleepers. Moreover, Cox proportional hazard analysis revealed that short sleep duration was a significant predictor of all-cause mortality (hazard ratio = 0.473; confidence interval 0.248-0.905, p = 0.024). Short sleep duration may serve as a prognostic indicator of mortality in Japanese patients with type 2 diabetes and may increase cardiovascular stress. Adequate sleep is essential for the management of type 2 diabetes. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Teduglutide, a novel glucagon-like peptide 2 analog, in the treatment of patients with short bowel syndrome

    DEFF Research Database (Denmark)

    Jeppesen, Palle Bekker

    2012-01-01

    Short bowel syndrome results from surgical resection, congenital defect or disease-associated loss of absorption. Parenteral support (PS) is lifesaving in patients with short bowel syndrome and intestinal failure who are unable to compensate for their malabsorption by metabolic or pharmacologic...... adaptation. Together, the symptoms of short bowel syndrome and the inconvenience and complications in relation to PS (e.g. catheter-related blood steam infections, central thrombosis and intestinal failure associated liver disease) may impair the quality of life of patients. The aim of treatment...... fluid absorption (and the concomitant reduction in diarrhea) and may be used in studies in which metabolic balance assessments are not performed. In studies of up to 24 weeks' duration, teduglutide appears to be safe and well tolerated. Treatment with teduglutide was associated with enhancement...

  9. Short-chain consensus alpha-neurotoxin: a synthetic 60-mer peptide with generic traits and enhanced immunogenic properties.

    Science.gov (United States)

    de la Rosa, Guillermo; Corrales-García, Ligia L; Rodriguez-Ruiz, Ximena; López-Vera, Estuardo; Corzo, Gerardo

    2018-04-06

    The three-fingered toxin family and more precisely short-chain α-neurotoxins (also known as Type I α-neurotoxins) are crucial in defining the elapid envenomation process, but paradoxically, they are barely neutralized by current elapid snake antivenoms. This work has been focused on the primary structural identity among Type I neurotoxins in order to create a consensus short-chain α-neurotoxin with conserved characteristics. A multiple sequence alignment considering the twelve most toxic short-chain α-neurotoxins reported from the venoms of the elapid genera Acanthophis, Oxyuranus, Walterinnesia, Naja, Dendroaspis and Micrurus led us to propose a short-chain consensus α-neurotoxin, here named ScNtx. The synthetic ScNtx gene was de novo constructed and cloned into the expression vector pQE30 containing a 6His-Tag and an FXa proteolytic cleavage region. Escherichia coli Origami cells transfected with the pQE30/ScNtx vector expressed the recombinant consensus neurotoxin in a soluble form with a yield of 1.5 mg/L of culture medium. The 60-amino acid residue ScNtx contains canonical structural motifs similar to α-neurotoxins from African elapids and its LD 50 of 3.8 µg/mice is similar to the most toxic short-chain α-neurotoxins reported from elapid venoms. Furthermore, ScNtx was also able to antagonize muscular, but not neuronal, nicotinic acetylcholine receptors (nAChR). Rabbits immunized with ScNtx were able to immune-recognize short-chain α-neurotoxins within whole elapid venoms. Type I neurotoxins are difficult to isolate and purify from natural sources; therefore, the heterologous expression of molecules such ScNtx, bearing crucial motifs and key amino acids, is a step forward to create common immunogens for developing cost-effective antivenoms with a wider spectrum of efficacy, quality and strong therapeutic value.

  10. Clinical trial simulations in pediatric patients using realistic covariates: application to teduglutide, a glucagon-like peptide-2 analog in neonates and infants with short-bowel syndrome.

    Science.gov (United States)

    Mouksassi, M S; Marier, J F; Cyran, J; Vinks, A A

    2009-12-01

    Teduglutide, a synthetic glucagon-like peptide-2 (GLP-2) analog with activity relating to the regeneration, maintenance, and repair of the intestinal epithelium, is currently being evaluated for the treatment of short-bowel syndrome (SBS), Crohn's disease, and other gastrointestinal disorders. On the basis of promising results from teduglutide studies in adults with SBS and from studies in neonatal and juvenile animal models, a pediatric multiple-dose phase I clinical study was designed to determine the safety, efficacy, and pharmacokinetics of teduglutide in pediatric patients with SBS who have undergone resection for necrotizing enterocolitis, malrotation, or intestinal atresia. This report details the application of clinical trial simulations coupled with a novel approach using generalized additive modeling for location, scale, and shape (GAMLSS) that facilitates the simulation of demographic covariates specific to the targeted patient populations. The goal was to optimize phase I dosing strategies and the likelihood of achieving target exposure and therapeutic effect.

  11. Short-acting glucagon-like peptide-1 receptor agonists as add-on to insulin therapy in type 1 diabetes

    DEFF Research Database (Denmark)

    Albèr, Anders; Brønden, Andreas; Knop, Filip K

    2017-01-01

    , which is associated with well-described and unfortunate adverse effects such as hypoglycaemia and increased body weight. Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) are the focus of increasing interest as a possible adjunctive treatment to insulin in type 1 diabetes because...... of their glucagonostatic and extrapancreatic effects. So far, the focus has mainly been on the long-acting GLP-1RAs, but the risk-benefit ratio emerging from studies evaluating the effect of long-acting GLP-1RAs as adjunctive therapy to insulin therapy in patients with type 1 diabetes has been disappointing. This might...... be attributable to a lack of glucagonostatic effect of these long-acting GLP-1RAs in type 1 diabetes, alongside development of tachyphylaxis to GLP-1-induced retardation of gastric emptying. In contrast, the short-acting GLP-1RAs seem to have a preserved and sustained effect on glucagon secretion and gastric...

  12. Effects of treatment with glucagon-like peptide-2 on bone resorption in colectomized patients with distal ileostomy or jejunostomy and short-bowel syndrome

    DEFF Research Database (Denmark)

    Gottschalck, Ida B; Jeppesen, Palle B; Hartmann, Bolette

    2008-01-01

    OBJECTIVE: The gut hormone GLP-2 (glucagon-like peptide-2) seems to be involved in the circadian pattern of bone resorption, whereas parathyroid hormone (PTH) is an established key hormone in bone turnover. Endogenous GLP-2 secretion is lacking in colectomized patients with short-bowel syndrome...... (SBS) and they have reduced bone mineral density (BMD). The aim of the study was to investigate the anti-resorptive effect (assessed by s-CTX) of 14 days of GLP-2 treatment in these patients and to determine whether 56 days of treatment would improve BMD. PTH secretion in response to GLP-2 was also...... in the SBS patients, and after 56 days of GLP-2 treatment there was no improvement in BMD. A significant reduction in PTH secretion in response to GLP-2 was observed only in patients with ileostomy. CONCLUSIONS: The decreased bone resorption in response to GLP-2 injections cannot be elicited in SBS patients...

  13. Optimization of the recombinant production and purification of a self-assembling peptide in Escherichia coli

    NARCIS (Netherlands)

    Rad-Malekshahi, Mazda; Flement, Matthias; Hennink, Wim E.; Mastrobattista, Enrico

    2014-01-01

    Background: Amphiphilic peptides are important building blocks to generate nanostructured biomaterials for drug delivery and tissue engineering applications. We have shown that the self-assembling peptide SA2 (Ac-AAVVLLLWEE) can be recombinantly produced in E. coli when fused to the small

  14. Induction of porcine host defense peptide gene expression by short-chain fatty acids and their analogs.

    Directory of Open Access Journals (Sweden)

    Xiangfang Zeng

    Full Text Available Dietary modulation of the synthesis of endogenous host defense peptides (HDPs represents a novel antimicrobial approach for disease control and prevention, particularly against antibiotic-resistant infections. However, HDP regulation by dietary compounds such as butyrate is species-dependent. To examine whether butyrate could induce HDP expression in pigs, we evaluated the expressions of a panel of porcine HDPs in IPEC-J2 intestinal epithelial cells, 3D4/31 macrophages, and primary monocytes in response to sodium butyrate treatment by real-time PCR. We revealed that butyrate is a potent inducer of multiple, but not all, HDP genes. Porcine β-defensin 2 (pBD2, pBD3, epididymis protein 2 splicing variant C (pEP2C, and protegrins were induced markedly in response to butyrate, whereas pBD1 expression remained largely unaltered in any cell type. Additionally, a comparison of the HDP-inducing efficacy among saturated free fatty acids of different aliphatic chain lengths revealed that fatty acids containing 3-8 carbons showed an obvious induction of HDP expression in IPEC-J2 cells, with butyrate being the most potent and long-chain fatty acids having only a marginal effect. We further investigated a panel of butyrate analogs for their efficacy in HDP induction, and found glyceryl tributyrate, benzyl butyrate, and 4-phenylbutyrate to be comparable with butyrate. Identification of butyrate and several analogs with a strong capacity to induce HDP gene expression in pigs provides attractive candidates for further evaluation of their potential as novel alternatives to antibiotics in augmenting innate immunity and disease resistance of pigs.

  15. A dose-equivalent comparison of the effects of continuous subcutaneous glucagon-like peptide 2 (GLP-2) infusions versus meal related GLP-2 injections in the treatment of short bowel syndrome (SBS) patients

    DEFF Research Database (Denmark)

    Naimi, R M; Madsen, K B; Askov-Hansen, C

    2013-01-01

    Glucagon-like peptide 2 (GLP-2), secreted endogenously from L-cells in the distal bowel in relation to meals, modulates intestinal absorption by adjusting gastric emptying and secretion and intestinal growth. Short bowel syndrome (SBS) patients with distal intestinal resections have attenuated...

  16. Fluctuations and structure of amphiphilic films; Fluctuations et structure de films d`amphiphiles

    Energy Technology Data Exchange (ETDEWEB)

    Gourier, CH

    1996-07-01

    This thesis is divided in three parts.The first part exposes in a theoretical point of view, how the fluctuations spectrum of an amphiphilic film is governed by its properties and its bidimensional characteristics.The measurements of fluctuations spectra of an interface are accessible with the measurement of intensity that interface diffuses out of the specular angle, we present in the second chapter the principles of the X rays diffusion by a real interface and see how the diffuse diffusion experiments allow to determine the fluctuations spectrum of an amphiphilic film. The second part is devoted to the different experimental techniques that have allowed to realize the study of fluctuation as well as the structural study.The third part is devoted to experimental results concerning the measurements of fluctuations spectra and to the study of the structure of amphiphilic films. We show that it is possible by using an intense source of X rays (ESRF: European Synchrotron Radiation Facility) to measure the water and amphiphilic films fluctuations spectra until molecular scales. The last chapter is devoted to the structural study and film fluctuations made of di-acetylenic molecules. (N.C.)

  17. Novel Tripod Amphiphiles for Membrane Protein Analysis

    DEFF Research Database (Denmark)

    Chae, Pil Seok; Kruse, Andrew C; Gotfryd, Kamil

    2013-01-01

    . The use of a detergent or other amphipathic agents is required to overcome the intrinsic incompatibility between the large lipophilic surfaces displayed by the membrane proteins in their native forms and the polar solvent molecules. Here, we introduce new tripod amphiphiles displaying favourable......Integral membrane proteins play central roles in controlling the flow of information and molecules across membranes. Our understanding of membrane protein structures and functions, however, is seriously limited, mainly due to difficulties in handling and analysing these proteins in aqueous solution...

  18. Effect of Amphiphiles on the Rheology of Triglyceride Networks

    Science.gov (United States)

    Seth, Jyoti

    2014-11-01

    Networks of aggregated crystallites form the structural backbone of many products from the food, cosmetic and pharmaceutical industries. Such materials are generally formulated by cooling a saturated solution to yield the desired solid fraction. Crystal nucleation and growth followed by aggregation leads to formation of a space percolating fractal-network. It is understood that microstructural hierarchy and particle-particle interactions determine material behavior during processing, storage and use. In this talk, rheology of suspensions of triglycerides (TAG, like tristearin) will be explored. TAGs exhibit a rich assortment of polymorphs and form suspensions that are evidently sensitive to surface modifying additives like surfactants and polymers. Here, a theoretical framework will be presented for suspensions containing TAG crystals interacting via pairwise potentials. The work builds on existing models of fractal aggregates to understand microstructure and its correlation with material rheology. Effect of amphiphilic additives is derived through variation of particle-particle interactions. Theoretical predictions for storage modulus will be compared against experimental observations and data from the literature and micro structural predictions against microscopy. Such a theory may serve as a step towards predicting short and long-term behavior of aggregated suspensions formulated via crystallization.

  19. Facially amphiphilic thiol capped gold and silver nanoparticles

    Indian Academy of Sciences (India)

    Abstract. A series of bile acid-derived facially amphiphilic thiols have been used to cap sliver and gold nanoparticles. The self-assembling properties of these steroid-capped nanoparticles have been investigated and reported in this article.

  20. Short-term sleep deprivation with nocturnal light exposure alters time-dependent glucagon-like peptide-1 and insulin secretion in male volunteers.

    Science.gov (United States)

    Gil-Lozano, Manuel; Hunter, Paola M; Behan, Lucy-Ann; Gladanac, Bojana; Casper, Robert F; Brubaker, Patricia L

    2016-01-01

    The intestinal L cell is the principal source of glucagon-like peptide-1 (GLP-1), a major determinant of insulin release. Because GLP-1 secretion is regulated in a circadian manner in rodents, we investigated whether the activity of the human L cell is also time sensitive. Rhythmic fluctuations in the mRNA levels of canonical clock genes were found in the human NCI-H716 L cell model, which also showed a time-dependent pattern in their response to well-established secretagogues. A diurnal variation in GLP-1 responses to identical meals (850 kcal), served 12 h apart in the normal dark (2300) and light (1100) periods, was also observed in male volunteers maintained under standard sleep and light conditions. These findings suggest the existence of a daily pattern of activity in the human L cell. Moreover, we separately tested the short-term effects of sleep deprivation and nocturnal light exposure on basal and postprandial GLP-1, insulin, and glucose levels in the same volunteers. Sleep deprivation with nocturnal light exposure disrupted the melatonin and cortisol profiles and increased insulin resistance. Moreover, it also induced profound derangements in GLP-1 and insulin responses such that postprandial GLP-1 and insulin levels were markedly elevated and the normal variation in GLP-1 responses was abrogated. These alterations were not observed in sleep-deprived participants maintained under dark conditions, indicating a direct effect of light on the mechanisms that regulate glucose homeostasis. Accordingly, the metabolic abnormalities known to occur in shift workers may be related to the effects of irregular light-dark cycles on these glucoregulatory pathways. Copyright © 2016 the American Physiological Society.

  1. The π Configuration of the WWW Motif of a Short Trp-Rich Peptide Is Critical for Targeting Bacterial Membranes, Disrupting Preformed Biofilms, and Killing Methicillin-Resistant Staphylococcus aureus.

    Science.gov (United States)

    Zarena, D; Mishra, Biswajit; Lushnikova, Tamara; Wang, Fangyu; Wang, Guangshun

    2017-08-08

    Tryptophan-rich peptides, being short and suitable for large-scale chemical synthesis, are attractive candidates for developing a new generation of antimicrobials to combat antibiotic-resistant bacteria (superbugs). Although there are numerous pictures of the membrane-bound structure of a single tryptophan (W), how multiple Trp amino acids assemble themselves and interact with bacterial membranes is poorly understood. This communication presents the three-dimensional structure of an eight-residue Trp-rich peptide (WWWLRKIW-NH 2 with 50% W) determined by the improved two-dimensional nuclear magnetic resonance method, which includes the measurements of 13 C and 15 N chemical shifts at natural abundance. This peptide forms the shortest two-turn helix with a distinct amphipathic feature. A unique structural arrangement is identified for the Trp triplet, WWW, that forms a π configuration with W2 as the horizontal bar and W1/W3 forming the two legs. An arginine scan reveals that the WWW motif is essential for killing methicillin-resistant Staphylococcus aureus USA300 and disrupting preformed bacterial biofilms. This unique π configuration for the WWW motif is stabilized by aromatic-aromatic interactions as evidenced by ring current shifts as well as nuclear Overhauser effects. Because the WWW motif is maintained, a change of I7 to R led to a potent antimicrobial and antibiofilm peptide with 4-fold improvement in cell selectivity. Collectively, this study elucidated the structural basis of antibiofilm activity of the peptide, identified a better peptide candidate via structure-activity relationship studies, and laid the foundation for engineering future antibiotics based on the WWW motif.

  2. Antiviral activity of cationic amphiphilic drugs.

    Science.gov (United States)

    Salata, Cristiano; Calistri, Arianna; Parolin, Cristina; Baritussio, Aldo; Palù, Giorgio

    2017-05-01

    Emerging and reemerging viral infections represent a major concern for human and veterinary public health and there is an urgent need for the development of broad-spectrum antivirals. Areas covered: A recent strategy in antiviral research is based on the identification of molecules targeting host functions required for infection of multiple viruses. A number of FDA-approved drugs used to treat several human diseases are cationic amphiphilic drugs (CADs) that have the ability to accumulate inside cells affecting several structures/functions hijacked by viruses during infection. In this review we summarized the CADs' chemical properties and effects on the cells and reported the main FDA-approved CADs that have been identified so far as potential antivirals in drug repurposing studies. Expert commentary: Although there have been concerns regarding the efficacy and the possible side effects of the off-label use of CADs as antivirals, they seem to represent a promising starting point for the development of broad-spectrum antiviral strategies. Further knowledge about their mechanism of action is required to improve their antiviral activity and to reduce the risk of side effects.

  3. Repurposing Cationic Amphiphilic Antihistamines for Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Anne-Marie Ellegaard

    2016-07-01

    Full Text Available Non-small cell lung cancer (NSCLC is one of the deadliest cancers worldwide. In search for new NSCLC treatment options, we screened a cationic amphiphilic drug (CAD library for cytotoxicity against NSCLC cells and identified several CAD antihistamines as inducers of lysosomal cell death. We then performed a cohort study on the effect of CAD antihistamine use on mortality of patients diagnosed with non-localized cancer in Denmark between 1995 and 2011. The use of the most commonly prescribed CAD antihistamine, loratadine, was associated with significantly reduced all-cause mortality among patients with non-localized NSCLC or any non-localized cancer when compared with use of non-CAD antihistamines and adjusted for potential confounders. Of the less frequently described CAD antihistamines, astemizole showed a similar significant association with reduced mortality as loratadine among patients with any non-localized cancer, and ebastine use showed a similar tendency. The association between CAD antihistamine use and reduced mortality was stronger among patients with records of concurrent chemotherapy than among those without such records. In line with this, sub-micromolar concentrations of loratadine, astemizole and ebastine sensitized NSCLC cells to chemotherapy and reverted multidrug resistance in NSCLC, breast and prostate cancer cells. Thus, CAD antihistamines may improve the efficacy of cancer chemotherapy.

  4. Repurposing Cationic Amphiphilic Antihistamines for Cancer Treatment.

    Science.gov (United States)

    Ellegaard, Anne-Marie; Dehlendorff, Christian; Vind, Anna C; Anand, Atul; Cederkvist, Luise; Petersen, Nikolaj H T; Nylandsted, Jesper; Stenvang, Jan; Mellemgaard, Anders; Østerlind, Kell; Friis, Søren; Jäättelä, Marja

    2016-07-01

    Non-small cell lung cancer (NSCLC) is one of the deadliest cancers worldwide. In search for new NSCLC treatment options, we screened a cationic amphiphilic drug (CAD) library for cytotoxicity against NSCLC cells and identified several CAD antihistamines as inducers of lysosomal cell death. We then performed a cohort study on the effect of CAD antihistamine use on mortality of patients diagnosed with non-localized cancer in Denmark between 1995 and 2011. The use of the most commonly prescribed CAD antihistamine, loratadine, was associated with significantly reduced all-cause mortality among patients with non-localized NSCLC or any non-localized cancer when compared with use of non-CAD antihistamines and adjusted for potential confounders. Of the less frequently described CAD antihistamines, astemizole showed a similar significant association with reduced mortality as loratadine among patients with any non-localized cancer, and ebastine use showed a similar tendency. The association between CAD antihistamine use and reduced mortality was stronger among patients with records of concurrent chemotherapy than among those without such records. In line with this, sub-micromolar concentrations of loratadine, astemizole and ebastine sensitized NSCLC cells to chemotherapy and reverted multidrug resistance in NSCLC, breast and prostate cancer cells. Thus, CAD antihistamines may improve the efficacy of cancer chemotherapy. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  5. Dissolving Microneedle Arrays for Transdermal Delivery of Amphiphilic Vaccines.

    Science.gov (United States)

    An, Myunggi; Liu, Haipeng

    2017-07-01

    Amphiphilic vaccine based on lipid-polymer conjugates is a new type of vaccine capable of self-delivering to the immune system. When injected subcutaneously, amphiphilic vaccines efficiently target antigen presenting cells in the lymph nodes (LNs) via a unique albumin-mediated transport and uptake mechanism and induce potent humoral and cellular immune responses. However, whether this new type of vaccine can be administrated via a safe, convenient microneedle-based transdermal approach remains unstudied. For such skin barrier-disruption systems, a simple application of microneedle arrays (MNs) is desired to disrupt the stratum corneum, and for rapid and pain-free self-administration of vaccines into the skin, the anatomic place permeates with an intricate mesh of lymphatic vessels draining to LNs. Here the microneedle transdermal approach is combined with amphiphilic vaccines to create a simple delivery approach which efficiently traffic molecular vaccines into lymphatics and draining LNs. The rapid release of amphiphilic vaccines into epidermis upon application of dissolving MNs to the skin of mice generates potent cellular and humoral responses, comparable or superior to those elicited by traditional needle-based immunizations. The results suggest that the amphiphilic vaccines delivered by dissolving MNs can provide a simple and safer vaccination method with enhanced vaccine efficacy. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. The designer leptin antagonist peptide Allo-aca compensates for short serum half-life with very tight binding to the receptor.

    Science.gov (United States)

    Otvos, Laszlo; Vetter, Stefan W; Koladia, Mohit; Knappe, Daniel; Schmidt, Rico; Ostorhazi, Eszter; Kovalszky, Ilona; Bionda, Nina; Cudic, Predrag; Surmacz, Eva; Wade, John D; Hoffmann, Ralf

    2014-04-01

    The leptin receptor antagonist peptide Allo-aca exhibits picomolar activities in various cellular systems and sub-mg/kg subcutaneous efficacies in animal models making it a prime drug candidate and target validation tool. Here we identified the biochemical basis for its remarkable in vivo activity. Allo-aca decomposed within 30 min in pooled human serum and was undetectable beyond the same time period from mouse plasma during pharmacokinetic measurements. The C max of 8.9 μg/mL at 5 min corresponds to approximately 22% injected peptide present in the circulation. The half-life was extended to over 2 h in bovine vitreous fluid and 10 h in human tears suggesting potential efficacy in ophthalmic diseases. The peptide retained picomolar anti-proliferation activity against a chronic myeloid leukemia cell line; addition of a C-terminal biotin label increased the IC50 value by approximately 200-fold. In surface plasmon resonance assays with the biotin-labeled peptide immobilized to a NeutrAvidin-coated chip, Allo-aca exhibited exceptionally tight binding to the binding domain of the human leptin receptor with ka = 5 × 10(5) M(-1) s(-1) and kdiss = 1.5 × 10(-4) s(-1) values. Peptides excel in terms of high activity and selectivity to their targets, and may activate or inactivate receptor functions considerably longer than molecular turnovers that take place in experimental animals.

  7. Dataset of the molecular dynamics simulations of bilayers consisting of short amyloidogenic peptide VDSWNVLVAG from Bgl2p–glucantransferase of S. cerevisiae cell wall

    Directory of Open Access Journals (Sweden)

    Anna V. Glyakina

    2016-12-01

    Full Text Available The amyloidogenic peptide VDSWNVLVAG from Bgl2p–glucantransferase of Saccharomyces cerevisiae cell wall and its modifying analog VESWNVLVAG were taken for the construction of four types of bilayers which differ by orientation of the peptides in the layers and of the layers relative to each other. These bilayers were used as starting models for the molecular dynamics (MD at three charge states (neutral, pH3, and pH5. The changes of the fraction of secondary structure during 1 ns simulations were received for 96 MD trajectories. The data article contains the necessary information for the construction of models of β-strands organization in the oligomer structure. These results were used in the associated research article “Structural model of amyloid fibrils for amyloidogenic peptide from Bgl2p–glucantransferase of S. cerevisiae cell wall and its modifying analog. New morphology of amyloid fibrils” (Selivanova et al., 2016 [1].

  8. Dual targeting strategy of magnetic nanoparticle-loaded and RGD peptide-activated stimuli-sensitive polymeric micelles for delivery of paclitaxel

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Meng Meng [Tsinghua University, Department of Chemical Engineering (China); Kang, Yoon Joong [Jungwon University, Department of Biomedical Science (Korea, Republic of); Sohn, Youngjoo [Kyung Hee University, Department of Anatomy, College of Korean Medicine (Korea, Republic of); Kim, Do Kyung, E-mail: eurokorean@gmail.com, E-mail: dokyung@konyang.ac.kr [Konyang University, Industry Cooperation Foundation (Korea, Republic of)

    2015-06-15

    A double targeting strategy of anti-neoplastic agent paclitaxel (PTX) was developed by incorporating magnetic nanoparticles and RGD peptide for enhanced cell cytotoxicity effect at lower dosage. A dual targeting mechanism including magnetic targeting and RGD ligand-specific targeting enhanced the overall cytotoxicity and reduced the effective dosage of PTX to achieve enhanced and sustained release of PTX in vitro. We addressed the issues of water-insolubility of oleic acid (OA)-stabilized SPIONs and low incorporation efficiency of hydrophobic PTX with SPION nanocarriers by using an amphiphilic polymer poly[(N-isopropylacrylamide-r-acrylamide)-b-l-lactic acid] (PNAL) as micelle-forming materials. A targeting moiety, GGGGRGD peptide, a RGD sequence-containing peptide with a short linker, is attached to the surface of PNAL-SPIONs via a homo-crosslinker. Confocal microscopy image analysis revealed that the cellular uptake was increased from (1.5 ± 0.5 % (PNAL) to 11.7 ± 0.8 % (RGD-PNAL-SPIONs) at 6 h incubation, once both RGD peptide and magnetic force attraction were incorporated into the carriers. Such multi-targeting nanocarriers showed promising potential in cancer-oriented diagnosis and therapy.

  9. Glucagon-like peptide-2 stimulates mucosal microcirculation measured by laser Doppler flowmetry in end-jejunostomy short bowel syndrome patients

    DEFF Research Database (Denmark)

    Høyerup, P; Hellström, P M; Schmidt, P T

    2013-01-01

    In animal and human studies glucagon-like peptide-2 (GLP-2) has been shown to increase blood flow in the superior mesenteric artery and the portal vein. This study describes the effect of GLP-2 measured directly on the intestinal mucosal blood flow by laser Doppler flowmetry (LDF) in end-jejunost......In animal and human studies glucagon-like peptide-2 (GLP-2) has been shown to increase blood flow in the superior mesenteric artery and the portal vein. This study describes the effect of GLP-2 measured directly on the intestinal mucosal blood flow by laser Doppler flowmetry (LDF) in end...

  10. Tough Amphiphilic Gels for Antifouling Applications

    Science.gov (United States)

    Villada, Laura M.

    Biofouling is the attachment of unwanted organisms on a surface, and it is influenced by a host of variables including the chemistry of the material as well as both the surface and bulk properties, and controlling and understanding the effect of these properties is critical for the development of effective materials to combat biofouling. All surfaces that are submerged in water are subject to the rapid colonization of a wide range of marine organisms. Marine biofouling decreases fuel efficiency, costing the Navy millions of dollars in penalty, as well as having drastic environmental effects. Previous prevention of biofouling in marine systems has been accomplished by the administration of biocides and toxic coatings. In recent years, increased concerns about the impacts of these hazardous compounds into marine ecosystems has spurred efforts to develop cost effective, non-toxic, and durable anti-fouling coatings. Hydrogels, hydrophilic crosslinked networks, are being used to modify silicone marine coatings and have demonstrated potential at combatting biofouling. Understanding the impact of amphiphilic materials, i.e. their structure and properties, on biofouling is of great importance in order to address the need in the industry. In this study, poly(2-hydroxyethyl methacrylate) (HEMA) crosslinked networks were tailored to investigate the influence of their surface and bulk properties on biofouling. Previous research utilizing HEMA-siloxane gels suggested a relationship between molecular weight between crosslinks, M c, and the attachment of soft fouling sporelings of the green algae U. linza and adsorption of the protein bovine serum albumin (BSA), and the initial thrust of this dissertation was aimed at resolving this relationship. Gel composition was modified by varying the siloxane crosslinking agent and the siloxane hydrophobic monomer concentrations. The gels exhibited an increase in elastic modulus from 0.17 to 8.55 MPa that coincided with an increasing

  11. Ionization of amphiphilic acidic block copolymers.

    Science.gov (United States)

    Colombani, Olivier; Lejeune, Elise; Charbonneau, Céline; Chassenieux, Christophe; Nicolai, Taco

    2012-06-28

    The ionization behavior of an amphiphilic diblock copolymer poly(n-butyl acrylate(50%)-stat-acrylic acid(50%))(100)-block-poly(acrylic acid)(100) (P(nBA(50%)-stat-AA(50%))(100)-b-PAA(100), DH50) and of its equivalent triblock copolymer P(nBA(50%)-stat-AA(50%))(100)-b-PAA(200)-b-P(nBA(50%)-stat-AA(50%))(100) (TH50) were studied by potentiometric titration either in pure water or in 0.5 M NaCl. These polymers consist of a hydrophilic acidic block (PAA) connected to a hydrophobic block, P(nBA(50%)-stat-AA(50%))(100), whose hydrophobic character has been mitigated by copolymerization with hydrophilic units. We show that all AA units, even those in the hydrophobic block could be ionized. However, the AA units within the hydrophobic block were less acidic than those in the hydrophilic block, resulting in the preferential ionization of the latter block. The preferential ionization of PAA over that of P(nBA(50%)-stat-AA(50%))(100) was stronger at higher ionic strength. Remarkably, the covalent bonds between the PAA and P(nBA(50%)-stat-AA(50%))(100) blocks in the diblock or the triblock did not affect the ionization of each block, although the self-association of the block copolymers into spherical aggregates modified the environment of the PAA blocks compared to when PAA was molecularly dispersed.

  12. Amphiphilic block copolymers for drug delivery.

    Science.gov (United States)

    Adams, Monica L; Lavasanifar, Afsaneh; Kwon, Glen S

    2003-07-01

    Amphiphilic block copolymers (ABCs) have been used extensively in pharmaceutical applications ranging from sustained-release technologies to gene delivery. The utility of ABCs for delivery of therapeutic agents results from their unique chemical composition, which is characterized by a hydrophilic block that is chemically tethered to a hydrophobic block. In aqueous solution, polymeric micelles are formed via the association of ABCs into nanoscopic core/shell structures at or above the critical micelle concentration. Upon micellization, the hydrophobic core regions serve as reservoirs for hydrophobic drugs, which may be loaded by chemical, physical, or electrostatic means, depending on the specific functionalities of the core-forming block and the solubilizate. Although the Pluronics, composed of poly(ethylene oxide)-block-poly(propylene oxide)-block-poly(ethylene oxide), are the most widely studied ABC system, copolymers containing poly(L-amino acid) and poly(ester) hydrophobic blocks have also shown great promise in delivery applications. Because each ABC has unique advantages with respect to drug delivery, it may be possible to choose appropriate block copolymers for specific purposes, such as prolonging circulation time, introduction of targeting moieties, and modification of the drug-release profile. ABCs have been used for numerous pharmaceutical applications including drug solubilization/stabilization, alteration of the pharmacokinetic profile of encapsulated substances, and suppression of multidrug resistance. The purpose of this minireview is to provide a concise, yet detailed, introduction to the use of ABCs and polymeric micelles as delivery agents as well as to highlight current and past work in this area. Copyright 2003 Wiley-Liss, Inc. and the American Pharmacists Association

  13. Magnetic Amphiphilic Composites Applied for the Treatment of Biodiesel Wastewaters

    Directory of Open Access Journals (Sweden)

    Bruno R. S. Lemos

    2012-05-01

    Full Text Available In this work, new magnetic amphiphilic composites were prepared by chemical vapor deposition with ethanol on the surface of hydrophilic natural chrysotile matrix containing Fe catalyst. XRD, Raman, Mössbauer and SEM analyses suggest the formation of a complex nanostructured material composed of hydrophobic carbon nanotubes/nanofibers grown on the hydrophilic surface of the MgSi fiber mineral and the presence of Fe metallic nanoparticles coated by carbon. These nanostructured particles show amphiphilic properties and interact very well with both oil and aqueous phases. When added to emulsions the amphiphilic particles locate on the oil/water interface and, under a magnetic field, the oil droplets collapsed leading to the separation of the aqueous and oil phases. Preliminary work showed excellent results on the use of these particles to break wastewater emulsions in the biodiesel process.

  14. Synthesis of silver nanoparticles in melts of amphiphilic polyesters

    Science.gov (United States)

    Vasylyev, S.; Damm, C.; Segets, D.; Hanisch, M.; Taccardi, N.; Wasserscheid, P.; Peukert, W.

    2013-03-01

    The current work presents a one-step procedure for the synthesis of amphiphilic silver nanoparticles suitable for production of silver-filled polymeric materials. This solvent free synthesis via reduction of Tollens’ reagent as silver precursor in melts of amphiphilic polyesters consisting of hydrophilic poly(ethylene glycol) blocks and hydrophobic alkyl chains allows the production of silver nanoparticles without any by-product formation. This makes them especially interesting for the production of medical devices with antimicrobial properties. In this article the influences of the chain length of the hydrophobic block in the amphiphilic polyesters and the process temperature on the particle size distribution (PSD) and the stability of the particles against agglomeration are discussed. According to the results of spectroscopic and viscosimetric investigations the silver precursor is reduced to elemental silver nanoparticles by a single electron transfer process from the poly(ethylene glycol) chain to the silver ion.

  15. Progress Toward the Clinical Translation of Bioinspired Peptide and Protein Assemblies.

    Science.gov (United States)

    Hainline, Kelly M; Fries, Chelsea N; Collier, Joel H

    2018-03-01

    Supramolecular materials composed of proteins and peptides have been receiving considerable attention toward a range of diseases and conditions from vaccines to drug delivery. Owing to the relative newness of this class of materials, the bulk of work to date has been preclinical. However, examples of approved treatments particularly in vaccines, dentistry, and hemostasis demonstrate the translational potential of supramolecular polypeptides. Critical milestones in the clinical development of this class of materials and currently approved supramolecular polypeptide therapies are described in this study. Additional examples of not-yet-approved materials that are steadily advancing toward clinical use are also featured. Spherical assemblies such as virus-like particles, designed protein nanoparticles, and spherical peptide amphiphiles are highlighted, followed by fiber-forming systems such as fibrillizing peptides, fiber-forming peptide-amphiphiles, and filamentous bacteriophages. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Conformation and intermolecular interactions of SA2 peptides self-assembled into vesicles.

    NARCIS (Netherlands)

    van Hell, A.J.; Klymchenko, A.; Burgers, P.P.; Moret, E.E.; Jiskoot, W.; Hennink, W.E.; Crommelin, D.J.A.; Mastrobattista, E.

    2010-01-01

    Previously we have shown that the recombinantly produced SA2 amphiphilic oligopeptide (Ac-Ala-Ala-Val-Val-Leu-Leu-Leu-Trp-Glu-Glu-COOH) self-assembles into nanovesicles (van Hell et al. 2007). In this study, the intermolecular interactions that contribute to the formation of such peptide vesicles

  17. Amphiphile Meets Amphiphile: Beyond the Polar-Apolar Dualism in Ionic Liquid/Alcohol Mixtures.

    Science.gov (United States)

    Russina, Olga; Sferrazza, Alessio; Caminiti, Ruggero; Triolo, Alessandro

    2014-05-15

    The mesoscopic morphology of binary mixtures of ethylammonium nitrate (EAN), the protic ionic liquid par excellence, and methanol is explored using neutron/X-ray diffraction and computational techniques. Both compounds are amphiphilic and characterized by an extended hydrogen bonding network: surprisingly, though macroscopically homogeneous, these mixtures turn out to be mesoscopically highly heterogeneous. Our study reveals that even in methanol-rich mixtures, a wide distribution of clusters exists where EAN preserves its bulk, sponge-like morphology. Accordingly methanol does not succeed in fully dissociating the ionic liquid that keeps on organizing in a bulk-like fashion. This behavior represents the premises to the more dramatic phenomenology observed with longer alcohols that eventually phase separate from EAN. These results challenge the commonly accepted polar and apolar moieties segregation in ionic liquids/molecular liquids mixtures and the current understanding of technologically relevant solvation processes.

  18. Coating of reverse osmosis membranes with amphiphilic copolymers for biofouling control

    KAUST Repository

    Bucs, Szilard

    2017-05-30

    Surface coating of membranes may be a promising option to control biofilm development and biofouling impact on membrane performance of spiral-wound reverse osmosis (RO) systems. The objective of this study was to investigate the impact of an amphiphilic copolymer coating on biofilm formation and biofouling control. The coating was composed of both hydrophilic and hydrophobic monomers hydroxyethyl methacrylate (HEMA) and perfluorodecyl acrylate (PFA), respectively. Commercial RO membranes were coated with HEMA-PFA copolymer film. Long and short term biofouling studies with coated and uncoated membranes and feed spacer were performed using membrane fouling simulators (MFSs) operated in parallel, fed with water containing nutrients. For the long-term studies pressure drop development in time was monitored and after eight days the MFSs were opened and the accumulated biofilm on the membrane and spacer sheets was quantified and characterized. The presence of the membrane coating was determined using X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR). Results showed that the amphiphilic coating (i) delayed biofouling (a lower pressure drop increase by a factor of 3 and a lower accumulated active biomass amount by a factor of 6), (ii) influenced the biofilm composition (23% lower polysaccharides and 132% higher protein content) and (iii) was still completely present on the membrane at the end of the biofouling study, showing that the coating was strongly attached to the membrane surface. Using coated membranes and feed spacers in combination with advanced cleaning strategies may be a suitable way to control biofouling.

  19. Bioactive self-assembled peptide nanofibers for corneal stroma regeneration.

    Science.gov (United States)

    Uzunalli, G; Soran, Z; Erkal, T S; Dagdas, Y S; Dinc, E; Hondur, A M; Bilgihan, K; Aydin, B; Guler, M O; Tekinay, A B

    2014-03-01

    Defects in the corneal stroma caused by trauma or diseases such as macular corneal dystrophy and keratoconus can be detrimental for vision. Development of therapeutic methods to enhance corneal regeneration is essential for treatment of these defects. This paper describes a bioactive peptide nanofiber scaffold system for corneal tissue regeneration. These nanofibers are formed by self-assembling peptide amphiphile molecules containing laminin and fibronectin inspired sequences. Human corneal keratocyte cells cultured on laminin-mimetic peptide nanofibers retained their characteristic morphology, and their proliferation was enhanced compared with cells cultured on fibronectin-mimetic nanofibers. When these nanofibers were used for damaged rabbit corneas, laminin-mimetic peptide nanofibers increased keratocyte migration and supported stroma regeneration. These results suggest that laminin-mimetic peptide nanofibers provide a promising injectable, synthetic scaffold system for cornea stroma regeneration. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  20. Crossing borders to bind proteins--a new concept in protein recognition based on the conjugation of small organic molecules or short peptides to polypeptides from a designed set.

    Science.gov (United States)

    Baltzer, Lars

    2011-06-01

    A new concept for protein recognition and binding is highlighted. The conjugation of small organic molecules or short peptides to polypeptides from a designed set provides binder molecules that bind proteins with high affinities, and with selectivities that are equal to those of antibodies. The small organic molecules or peptides need to bind the protein targets but only with modest affinities and selectivities, because conjugation to the polypeptides results in molecules with dramatically improved binder performance. The polypeptides are selected from a set of only sixteen sequences designed to bind, in principle, any protein. The small number of polypeptides used to prepare high-affinity binders contrasts sharply with the huge libraries used in binder technologies based on selection or immunization. Also, unlike antibodies and engineered proteins, the polypeptides have unordered three-dimensional structures and adapt to the proteins to which they bind. Binder molecules for the C-reactive protein, human carbonic anhydrase II, acetylcholine esterase, thymidine kinase 1, phosphorylated proteins, the D-dimer, and a number of antibodies are used as examples to demonstrate that affinities are achieved that are higher than those of the small molecules or peptides by as much as four orders of magnitude. Evaluation by pull-down experiments and ELISA-based tests in human serum show selectivities to be equal to those of antibodies. Small organic molecules and peptides are readily available from pools of endogenous ligands, enzyme substrates, inhibitors or products, from screened small molecule libraries, from phage display, and from mRNA display. The technology is an alternative to established binder concepts for applications in drug development, diagnostics, medical imaging, and protein separation.

  1. Facially amphiphilic thiol capped gold and silver nanoparticles

    Indian Academy of Sciences (India)

    Wintec

    Jawaharlal Nehru Centre for Advanced Scientific Research,. Bangalore 560 064. Facially amphiphilic thiol capped gold and silver nanoparticles. †. SHREEDHAR BHAT a and UDAY MAITRA*. Department of Organic Chemistry, Indian Institute of Science, Bangalore 560 012 a. Current address: ISM, University of Bordeaux, ...

  2. Blends of Amphiphilic, Hyperbranched Polyesters and Different Polyolefins

    NARCIS (Netherlands)

    Schmaljohann, D.; Pötschke, P.; Hässler, R.; Voit, B.I.; Froehling, P.E.; Mostert, B.; Loontjens, J.A.

    1999-01-01

    A hyperbranched polyester based on 3,5-dihydroxybenzoic acid was completely modified with dodecanoyl chloride to result in an amphiphilic, globular polymer, which has a polar core and a nonpolar outer sphere with the ability both to incorporate an organic dye and to interact with a nonpolar matrix.

  3. Photoresponsive Amphiphilic Macrocycles Containing Main-Chain Azobenzene Polymers.

    Science.gov (United States)

    Sun, Yadong; Wang, Zhao; Li, Yiwen; Zhang, Zhengbiao; Zhang, Wei; Pan, Xiangqiang; Zhou, Nianchen; Zhu, Xiulin

    2015-07-01

    Herein, the first example of photosensitive cyclic amphiphilic homopolymers consisting of multiple biphenyl azobenzene chromophores in the cyclic main chain tethered with hydrophilic tetraethylene glycol monomethyl ether units is presented. The synthetic approach involves sequentially performed thermal catalyzed "click" step-growth polymerization in bulk, and Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) intramolecular cyclization from α-alkyne/ω-azide linear precursors. It is observed that such amphiphilic macrocycles exhibit increased glass transition temperatures (Tg ), slightly faster trans-cis-trans photoisomerization, and enhanced fluorescence emission intensity compared with the corresponding linear polymers. In addition, the cyclic amphiphilic homopolymers self-assemble into spherical nanoparticles with smaller sizes which possess slower photoresponsive behaviors in a tetrahydrofuran/water mixture compared with those of the linear ones. All these interesting observations suggest that the cyclic topology has a great influence on the physical properties and self-assembly behavior of these photoresponsive amphiphilic macrocycles in general. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Facially amphiphilic thiol capped gold and silver nanoparticles

    Indian Academy of Sciences (India)

    Wintec

    *For correspondence. Also at the Chemical Biology Unit,. Jawaharlal Nehru Centre for Advanced Scientific Research,. Bangalore 560 064. Facially amphiphilic thiol capped gold and silver nanoparticles. †. SHREEDHAR BHAT a and UDAY MAITRA*. Department of Organic Chemistry, Indian Institute of Science, Bangalore ...

  5. Effects of perfluorinated amphiphiles on backward swimming in Paramecium caudatum

    International Nuclear Information System (INIS)

    Matsubara, Eriko; Harada, Kouji; Inoue, Kayoko; Koizumi, Akio

    2006-01-01

    PFOS and PFOA are ubiquitous contaminants in the environment. We investigated the effects of fluorochemicals on calcium currents in Paramecium caudatum using its behavioral changes. Negatively charged amphiphiles prolonged backward swimming (BWS) of Paramecium. PFOS significantly prolonged BWS, while PFOA was less potent (EC 5 : 29.8 ± 4.1 and 424.1 ± 124.0 μM, respectively). The BWS prolongation was blocked by cadmium, indicating that the cellular calcium conductance had been modified. The positively charged amphiphile FOSAPrTMA shortened BWS (EC 5 : 19.1 ± 17.3). Nonionic amphiphiles did not affect BWS. The longer-chain perfluorinated carboxylates PFNA and PFDA were more potent than PFOA (EC 5 : 98.7 ± 20.1 and 60.4 ± 10.1 μM, respectively). However, 1,8-perfluorooctanedioic acid and 1,10-perfluorodecanedioic acid did not prolong BWS. The critical micelle concentration (CMC) and BWS prolongation for negatively charged amphiphiles showed a clear correlation (r 2 = 0.8008, p < 0.001). In summary, several perfluorochemicals and PFOS and PFOA had similar effects in Paramecium, while chain length, CMC, and electric charge were major determinants of BWS duration

  6. Micellar structure of amphiphilic poly(2-oxazoline) diblock copolymers

    DEFF Research Database (Denmark)

    Papadakis, C.M.; Ivanova, R.; Lüdtke, K.

    2007-01-01

    Amphiphilic diblock copolymers from poly(2-oxazoline)s in aqueous solution can form micelles. By means of small-angle neutron scattering, we have found that poly[(n-nonyl-2-oxazoline)-b-(methyl-2-oxazoline)] {P[(NOx)-b-(MOx)]} diblock copolymers in aqueous solution form micelles of core-shell typ...

  7. Reinforcement of latex rubber by the incorporation of amphiphilic particles

    Science.gov (United States)

    Latex rubbers are fabricated from latex suspensions. During the fabrication process, latex particles are bound together while water is removed from the suspension. This report shows that the mechanical properties of latex rubbers can be improved by incorporating a small amount of amphiphilic submicr...

  8. Biocompatible Amphiphilic Hydrogel-Solid Dimer Particles as Colloidal Surfactants.

    Science.gov (United States)

    Chen, Dong; Amstad, Esther; Zhao, Chun-Xia; Cai, Liheng; Fan, Jing; Chen, Qiushui; Hai, Mingtan; Koehler, Stephan; Zhang, Huidan; Liang, Fuxin; Yang, Zhenzhong; Weitz, David A

    2017-12-26

    Emulsions of two immiscible liquids can slowly coalesce over time when stabilized by surfactant molecules. Pickering emulsions stabilized by colloidal particles can be much more stable. Here, we fabricate biocompatible amphiphilic dimer particles using a hydrogel, a strongly hydrophilic material, and achieve large contrast in the wetting properties of the two bulbs, resulting in enhanced stabilization of emulsions. We generate monodisperse single emulsions of alginate and shellac solution in oil using a flow-focusing microfluidics device. Shellac precipitates from water and forms a solid bulb at the periphery of the droplet when the emulsion is exposed to acid. Molecular interactions result in amphiphilic dimer particles that consist of two joined bulbs: one hydrogel bulb of alginate in water and the other hydrophobic bulb of shellac. Alginate in the hydrogel compartment can be cross-linked using calcium cations to obtain stable particles. Analogous to surfactant molecules at the interface, the resultant amphiphilic particles stand at the water/oil interface with the hydrogel bulb submerged in water and the hydrophobic bulb in oil and are thus able to stabilize both water-in-oil and oil-in-water emulsions, making these amphiphilic hydrogel-solid particles ideal colloidal surfactants for various applications.

  9. On the slowdown mechanism of water dynamics around small amphiphiles

    NARCIS (Netherlands)

    Homsi Brandeburgo, W.; Thijmen van der Post, S.; Meijer, E.J.; Ensing, B.

    2015-01-01

    Aqueous solvation of small amphiphilic molecules exhibits a unique and complex dynamics, that is only partially understood. A recent series of studies on the hydration of small organic compounds, such as tetramethylurea (TMU), trimethylamine N-oxide (TMAO) and urea, has provided strong evidence of a

  10. Modulated self-organization in complex amphiphilic systems

    NARCIS (Netherlands)

    Sevink, A; Zvelindovsky, A; Fraaije, H

    2000-01-01

    We discuss novel simulation methods for 3D pattern formation in complex amphiphilic systems. The focus is on the supra-molecular or mesoscopic level. The building blocks consist of sequences of dissimilar monomers, connected in copolymer chain molecules. Internal factors such as composition and

  11. Modulated self-organization in complex amphiphilic systems

    NARCIS (Netherlands)

    Fraaije, JGEM; Zvelindovsky, AV; Sevink, GJA; Maurits, NM

    2000-01-01

    We discuss novel simulation methods for 3D pattern formation in complex amphiphilic systems. The focus is on the supra-molecular or mesoscopic level. The building blocks consist of sequences of dissimilar monomers. connected in copolymer chain molecules. Internal factors such as composition and

  12. Nucleic acid amphiphiles : synthesis and self-assembled nanostructures

    NARCIS (Netherlands)

    Kwak, Minseok; Herrmann, Andreas; Clever, Guido; Mao, Chengde; Shionoya, Mitsuhiko; Stulz, Eugen

    2011-01-01

    This review provides an overview of a relatively new class of bio-conjugates, DNA amphiphiles, which consist of oligonucleotides covalently bonded to synthetic hydrophobic units. The reader will find the basic principles for the structural design and preparation methods of the materials. Moreover,

  13. Disorder and order in unfolded and disordered peptides and proteins: a view derived from tripeptide conformational analysis. II. Tripeptides with short side chains populating asx and β-type like turn conformations.

    Science.gov (United States)

    Rybka, Karin; Toal, Siobhan E; Verbaro, Daniel J; Mathieu, Daniel; Schwalbe, Harald; Schweitzer-Stenner, Reinhard

    2013-06-01

    In the preceding paper, we found that ensembles of tripeptides with long or bulky chains can include up to 20% of various turns. Here, we determine the structural and thermodynamic characteristics of GxG peptides with short polar and/or ionizable central residues (D, N, C), whose conformational distributions exhibit higher than average percentage (>20%) of turn conformations. To probe the side-chain conformations of these peptides, we determined the (3)J(H(α),H(β)) coupling constants and derived the population of three rotamers with χ1 -angles of -60°, 180° and 60°, which were correlated with residue propensities by DFT-calculations. For protonated GDG, the rotamer distribution provides additional evidence for asx-turns. A comparison of vibrational spectra and NMR coupling constants of protonated GDG, ionized GDG, and the protonated aspartic acid dipeptide revealed that side chain protonation increases the pPII content at the expense of turn populations. The charged terminal groups, however, have negligible influence on the conformational properties of the central residue. Like protonated GDG, cationic GCG samples asx-turns to a significant extent. The temperature dependence of the UVCD spectra and (3)J(H(N)H(α)) constants suggest that the turn populations of GDG and GNG are practically temperature-independent, indicating enthalpic and entropic stabilization. The temperature-independent J-coupling and UVCD spectra of GNG require a three-state model. Our results indicate that short side chains with hydrogen bonding capability in GxG segments of proteins may serve as hinge regions for establishing compact structures of unfolded proteins and peptides. Copyright © 2012 Wiley Periodicals, Inc.

  14. Screening Nylon-3 Polymers, a New Class of Cationic Amphiphiles, for siRNA Delivery

    Science.gov (United States)

    2015-01-01

    Amphiphilic nucleic acid carriers have attracted strong interest. Three groups of nylon-3 copolymers (poly-β-peptides) possessing different cationic/hydrophobic content were evaluated as siRNA delivery agents in this study. Their ability to condense siRNA was determined in SYBR Gold assays. Their cytotoxicity was tested by MTT assays, their efficiency of delivering Alexa Fluor-488-labeled siRNA intracellularly in the presence and absence of uptake inhibitors was assessed by flow cytometry, and their transfection efficacies were studied by luciferase knockdown in a cell line stably expressing luciferase (H1299/Luc). Endosomal release was determined by confocal laser scanning microscopy and colocalization with lysotracker. All polymers efficiently condensed siRNA at nitrogen-to-phosphate (N/P) ratios of 5 or lower, as reflected in hydrodynamic diameters smaller than that at N/P 1. Although several formulations had negative zeta potentials at N/P 1, G2C and G2D polyplexes yielded >80% uptake in H1299/Luc cells, as determined by flow cytometry. Luciferase knockdown (20–65%) was observed after transfection with polyplexes made of the high molecular weight polymers that were the most hydrophobic. The ability of nylon-3 polymers to deliver siRNA intracellularly even at negative zeta potential implies that they mediate transport across cell membranes based on their amphiphilicity. The cellular uptake route was determined to strongly depend on the presence of cholesterol in the cell membrane. These polymers are, therefore, very promising for siRNA delivery at reduced surface charge and toxicity. Our study identified nylon-3 formulations at low N/P ratios for effective gene knockdown, indicating that nylon-3 polymers are a new, promising type of gene delivery agent. PMID:25437915

  15. Screening nylon-3 polymers, a new class of cationic amphiphiles, for siRNA delivery.

    Science.gov (United States)

    Nadithe, Venkatareddy; Liu, Runhui; Killinger, Bryan A; Movassaghian, Sara; Kim, Na Hyung; Moszczynska, Anna B; Masters, Kristyn S; Gellman, Samuel H; Merkel, Olivia M

    2015-02-02

    Amphiphilic nucleic acid carriers have attracted strong interest. Three groups of nylon-3 copolymers (poly-β-peptides) possessing different cationic/hydrophobic content were evaluated as siRNA delivery agents in this study. Their ability to condense siRNA was determined in SYBR Gold assays. Their cytotoxicity was tested by MTT assays, their efficiency of delivering Alexa Fluor-488-labeled siRNA intracellularly in the presence and absence of uptake inhibitors was assessed by flow cytometry, and their transfection efficacies were studied by luciferase knockdown in a cell line stably expressing luciferase (H1299/Luc). Endosomal release was determined by confocal laser scanning microscopy and colocalization with lysotracker. All polymers efficiently condensed siRNA at nitrogen-to-phosphate (N/P) ratios of 5 or lower, as reflected in hydrodynamic diameters smaller than that at N/P 1. Although several formulations had negative zeta potentials at N/P 1, G2C and G2D polyplexes yielded >80% uptake in H1299/Luc cells, as determined by flow cytometry. Luciferase knockdown (20-65%) was observed after transfection with polyplexes made of the high molecular weight polymers that were the most hydrophobic. The ability of nylon-3 polymers to deliver siRNA intracellularly even at negative zeta potential implies that they mediate transport across cell membranes based on their amphiphilicity. The cellular uptake route was determined to strongly depend on the presence of cholesterol in the cell membrane. These polymers are, therefore, very promising for siRNA delivery at reduced surface charge and toxicity. Our study identified nylon-3 formulations at low N/P ratios for effective gene knockdown, indicating that nylon-3 polymers are a new, promising type of gene delivery agent.

  16. Synthesis, characterization, and utilization of polyol amphiphile molecules

    Science.gov (United States)

    Osenar, Paul

    1998-12-01

    Recent interest in self-organizing systems has led to the development of numerous novel molecules. This work describes the synthesis and characterization of a new type of amphiphile based on polar moieties of oligo(vinyl alcohol). The use of oligomeric moieties allows access to hydroxylated, nonionic amphiphiles beyond those available via the alkylation of various carbohydrates. Two synthetic pathways have been developed based on a precursor diblock structure of a hydrophobe and an oligo(vinyl ether) chain. The first methodology relies on aldol group transfer polymerization of various silyl vinyl ether monomers. In this method, a functionalized initiator was designed based on 4-hydroxybenzaldehyde in order to synthesize oligomers with a phenol terminus. Incorporation of a hydrophobic moiety was then accomplished via esterification to this terminus. A second approach to the precursor diblock was also developed based on direct initiation with a hydrophobe. Here, an aldehyde terminated hydrophobe was converted into an alpha-iodoether by reaction with trimethylsilyl iodide. In the presence of a Lewis acid catalyst, various alkyl vinyl ether oligomers can be grown from the hydrophobe via cationic polymerization techniques. These diblock structures can be converted to polyol amphiphiles by cleaving the ether side groups to yield a chain of hydroxyl groups. In the case of the silyl ethers, cleavage occurs with exposure to hydrofluoric acid; while those based on t-butyl ethers can be converted to silyl ethers with trimethylsilyl iodide and subsequently cleaved with fluoride ion. Polyol amphiphiles were synthesized with various hydroxyl chain lengths and hydrophobic moieties, including oleyl and oligo(styrene). These novel amphiphiles are predictably hygroscopic, forming lyotropic liquid crystals upon exposure to water. The resulting lamellar and hexagonal mesophases were characterized by a variety of techniques including small angle x-ray scattering and polarized optical

  17. Peptide dendrimers

    Czech Academy of Sciences Publication Activity Database

    Niederhafner, Petr; Šebestík, Jaroslav; Ježek, Jan

    2005-01-01

    Roč. 11, - (2005), 757-788 ISSN 1075-2617 R&D Projects: GA ČR(CZ) GA203/03/1362 Institutional research plan: CEZ:AV0Z40550506 Keywords : multiple antigen peptides * peptide dendrimers * synthetic vaccine * multipleantigenic peptides Subject RIV: CC - Organic Chemistry Impact factor: 1.803, year: 2005

  18. Preparation and Characterization of Amphiphilic Triblock Terpolymer-Based Nanofibers as Antifouling Biomaterials

    KAUST Repository

    Cho, Youngjin

    2012-05-14

    Antifouling surfaces are critical for the good performance of functional materials in various applications including water filtration, medical implants, and biosensors. In this study, we synthesized amphiphilic triblock terpolymers (tri-BCPs, coded as KB) and fabricated amphiphilic nanofibers by electrospinning of solutions prepared by mixing the KB with poly(lactic acid) (PLA) polymer. The resulting fibers with amphiphilic polymer groups exhibited superior antifouling performance to the fibers without such groups. The adsorption of bovine serum albumin (BSA) on the amphiphilic fibers was about 10-fold less than that on the control surfaces from PLA and PET fibers. With the increase of the KB content in the amphiphilic fibers, the resistance to adsorption of BSA was increased. BSA was released more easily from the surface of the amphiphilic fibers than from the surface of hydrophobic PLA or PET fibers. We have also investigated the structural conformation of KB in fibers before and after annealing by contact angle measurements, transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDX), and coarse-grained molecular dynamics (CGMD) simulation to probe the effect of amphiphilic chain conformation on antifouling. The results reveal that the amphiphilic KB was evenly distributed within as-spun hybrid fibers, while migrated toward the core from the fiber surface during thermal treatment, leading to the reduction in antifouling. This suggests that the antifouling effect of the amphiphilic fibers is greatly influenced by the arrangement of amphiphilic groups in the fibers. © 2012 American Chemical Society.

  19. Identification of a Short Cell-Penetrating Peptide from Bovine Lactoferricin for Intracellular Delivery of DNA in Human A549 Cells.

    Science.gov (United States)

    Liu, Betty R; Huang, Yue-Wern; Aronstam, Robert S; Lee, Han-Jung

    2016-01-01

    Cell-penetrating peptides (CPPs) have been shown to deliver cargos, including protein, DNA, RNA, and nanomaterials, in fully active forms into live cells. Most of the CPP sequences in use today are based on non-native proteins that may be immunogenic. Here we demonstrate that the L5a CPP (RRWQW) from bovine lactoferricin (LFcin), stably and noncovalently complexed with plasmid DNA and prepared at an optimal nitrogen/phosphate ratio of 12, is able to efficiently enter into human lung cancer A549 cells. The L5a CPP delivered a plasmid containing the enhanced green fluorescent protein (EGFP) coding sequence that was subsequently expressed in cells, as revealed by real-time PCR and fluorescent microscopy at the mRNA and protein levels, respectively. Treatment with calcium chloride increased the level of gene expression, without affecting CPP-mediated transfection efficiency. Zeta-potential analysis revealed that positively electrostatic interactions of CPP/DNA complexes correlated with CPP-mediated transport. The L5a and L5a/DNA complexes were not cytotoxic. This biomimetic LFcin L5a represents one of the shortest effective CPPs and could be a promising lead peptide with less immunogenic for DNA delivery in gene therapy.

  20. Development of polycationic amphiphilic cyclodextrin nanoparticles for anticancer drug delivery

    Directory of Open Access Journals (Sweden)

    Gamze Varan

    2017-07-01

    Full Text Available Background: Paclitaxel is a potent anticancer drug that is effective against a wide spectrum of cancers. To overcome its bioavailability problems arising from very poor aqueous solubility and tendency to recrystallize upon dilution, paclitaxel is commercially formulated with co-solvents such as Cremophor EL® that are known to cause serious side effects during chemotherapy. Amphiphilic cyclodextrins are favored oligosaccharides as drug delivery systems for anticancer drugs, having the ability to spontaneously form nanoparticles without surfactant or co-solvents. In the past few years, polycationic, amphiphilic cyclodextrins were introduced as effective agents for gene delivery in the form of nanoplexes. In this study, the potential of polycationic, amphiphilic cyclodextrin nanoparticles were evaluated in comparison to non-ionic amphiphilic cyclodextrins and core–shell type cyclodextrin nanoparticles for paclitaxel delivery to breast tumors. Pre-formulation studies were used as a basis for selecting the suitable organic solvent and surfactant concentration for the novel polycationic cyclodextrin nanoparticles. The nanoparticles were then extensively characterized with particle size distribution, polydispersity index, zeta potential, drug loading capacity, in vitro release profiles and cytotoxicity studies.Results: Paclitaxel-loaded cyclodextrin nanoparticles were obtained in the diameter range of 80−125 nm (depending on the nature of the cyclodextrin derivative where the smallest diameter nanoparticles were obtained with polycationic (PC βCDC6. A strong positive charge also helped to increase the loading capacity of the nanoparticles with paclitaxel up to 60%. Interestingly, cyclodextrin nanoparticles were able to stabilize paclitaxel in aqueous solution for 30 days. All blank cyclodextrin nanoparticles were demonstrated to be non-cytotoxic against L929 mouse fibroblast cell line. In addition, paclitaxel-loaded nanoparticles have a

  1. Perspectives and Peptides of the Next Generation

    Science.gov (United States)

    Brogden, Kim A.

    Shortly after their discovery, antimicrobial peptides from prokaryotes and eukaryotes were recognized as the next potential generation of pharmaceuticals to treat antibiotic-resistant bacterial infections and septic shock, to preserve food, or to sanitize surfaces. Initial research focused on identifying the spectrum of antimicrobial agents, determining the range of antimicrobial activities against bacterial, fungal, and viral pathogens, and assessing the antimicrobial activity of synthetic peptides versus their natural counterparts. Subsequent research then focused on the mechanisms of antimicrobial peptide activity in model membrane systems not only to identify the mechanisms of antimicrobial peptide activity in microorganisms but also to discern differences in cytotoxicity for prokaryotic and eukaryotic cells. Recent, contemporary work now focuses on current and future efforts to construct hybrid peptides, peptide congeners, stabilized peptides, peptide conjugates, and immobilized peptides for unique and specific applications to control the growth of microorganisms in vitro and in vivo.

  2. Differential effects of glucagon-like peptide-1 on microvascular recruitment and glucose metabolism in short- and long-term Insulin resistance

    DEFF Research Database (Denmark)

    Sjøberg, Kim Anker; Rattigan, Stephen; Jeppesen, Jacob Fuglsbjerg

    2015-01-01

    Acute infusion of glucagon-like-peptide-1 (GLP-1) has potent effects on blood flow distribution through the microcirculation in healthy humans and rats. High fat diet induces impairments in insulin-mediated microvascular recruitment (MVR) and muscle glucose uptake, and here we examined whether...... this could be reversed by GLP-1. Using contrast-enhanced ultrasound, microvascular recruitment was assessed by continuous real-time imaging of gas-filled microbubbles in the microcirculation after acute (5 days) and prolonged (8 weeks) high fat diet (HF) induced insulin resistance in rats. An euglycemic...... hyperinsulinemic clamp (3 mU·min(-1) ·kg(-1) ) with or without a co-infusion of GLP-1 (100 pmol·l(-1) ) was performed in anaesthetized rats. Consumption of the HF diet attenuated the insulin-mediated MVR in both 5 days and 8 weeks HF interventions which was associated with a 50% reduction in insulin...

  3. Diffusion of surface-active amphiphiles in silicone-based fouling-release coatings

    DEFF Research Database (Denmark)

    Noguer, Albert Camós; Olsen, S. M.; Hvilsted, Søren

    2017-01-01

    Amphiphiles (i.e. amphiphilic molecules such as surfactants, block copolymers and similar compounds) are used in small amounts to modify the surface properties of polymeric materials. In silicone fouling-release coatings, PEG-based amphiphiles are added to provide biofouling-resistance. The success...... of the amphiphiles shows a weak dependency on their molecular weight, although this dependency is much less pronounced than for other rubbery polymeric materials. The biofouling-resistance properties in fouling-release coatings were also studied for these amphiphiles. It was found that the diffusion coefficient does...... not have any influence on the biofouling-resistance results for the studied compounds. Instead, the chemistry of the hydrophobic block of the amphiphiles is much more significant, with PEG-PDMS block copolymers showing the best properties among the studied compounds....

  4. Magnetic Amphiphilic Composites Applied for the Treatment of Biodiesel Wastewaters

    OpenAIRE

    Bruno R. S. Lemos; Ana Paula C. Teixeira; José D. Ardisson; Waldemar A. A. Macedo; Luis E. Fernandez-Outon; Camila C. Amorim; Flávia C. C. Moura; Rochel M. Lago

    2012-01-01

    In this work, new magnetic amphiphilic composites were prepared by chemical vapor deposition with ethanol on the surface of hydrophilic natural chrysotile matrix containing Fe catalyst. XRD, Raman, Mössbauer and SEM analyses suggest the formation of a complex nanostructured material composed of hydrophobic carbon nanotubes/nanofibers grown on the hydrophilic surface of the MgSi fiber mineral and the presence of Fe metallic nanoparticles coated by carbon. These nanostructured particles show am...

  5. Relation between structure and organisation properties of new amphiphilic cyclodextrins

    International Nuclear Information System (INIS)

    Moutard, Stephane

    2003-01-01

    Since a number of years, special attention and efforts have been made to prepare amphiphilic cyclodextrins (CDs) with the objective to use them to obtain supramolecular assemblies as such or in the presence of preformed lipidic structures. The aim of these investigation is in both cases to combine the size specificity of cyclodextrins for guests and the transport properties of phospho-lipidic structures. The final objects could be of importance to transport or target biologically relevant molecules such as drugs using new galenic formulations. In a first step, a new family of amphiphilic CDs was prepared from a pure phospholipids (DMPE) onto cyclodextrins or methylated derivatives through a spacing arm. The afforded compounds (phospholipidyl-cyclodextrins) were fully characterized by high field NMR and high resolution mass spectrometry. The methylated derivatives were shown to self-organize in water with low CMC to form fluctuating micellar fibers retaining the inclusion capacity of the cyclodextrin cavities. The interactions of these compounds with membrane systems were investigated as black films using X-ray reflectivity and by evaluation of their detergent power towards model DMPC liposomes. Their ability to cross over the Blood Brain Barrier was evidenced by a new approach making use of novel immuno-enzymatic assays. In a second step, a new class of amphiphilic cyclodextrins was considered (peptidolipidyl-cyclodextrins). Although they are structurally similar to phospholipidyl-CDs, their preparation overcomes the tedious steps of the later and lead to a considerable versatility in terms of the number of possible molecules to be prepared. Moreover, the stability problems encountered with phospholipids are avoided. Several examples have been prepared, fully characterized and their organization properties investigated by the determination of CMC and by deuterium NMR on a pure and homogeneous mixed peptidolipidyl-CD / DMPC lamellar phase. This novel class of

  6. Nanorings from the self-assembly of amphiphilic molecular dumbbells.

    Science.gov (United States)

    Kim, Jung-Keun; Lee, Eunji; Huang, Zhegang; Lee, Myongsoo

    2006-11-01

    We have prepared amphiphilic dumbbell molecules consisting of hydrophobic alkyl chains and hydrophilic oligoether dendrons at each end of the rod segment. The molecular dumbbells, in aqueous solution, self-assemble into toroids as an intermediate nanostructure between spherical and long cylindrical micelles. The formation of toroidal structure is likely to originate from side by side connections of discrete bundles through the combination of strong hydrophobic interactions and anisotropic aggregation of rod segments.

  7. Recent Advances in the Chemistry of Glycoconjugate Amphiphiles.

    Science.gov (United States)

    Latxague, Laurent; Gaubert, Alexandra; Barthélémy, Philippe

    2018-01-02

    Glyconanoparticles essentially result from the (covalent or noncovalent) association of nanometer-scale objects with carbohydrates. Such glyconanoparticles can take many different forms and this mini review will focus only on soft materials (colloids, liposomes, gels etc.) with a special emphasis on glycolipid-derived nanomaterials and the chemistry involved for their synthesis. Also this contribution presents Low Molecular Weight Gels (LMWGs) stabilized by glycoconjugate amphiphiles. Such soft materials are likely to be of interest for different biomedical applications.

  8. Preparation and self-folding of amphiphilic DNA origami.

    Science.gov (United States)

    Zhou, Chao; Wang, Dianming; Dong, Yuanchen; Xin, Ling; Sun, Yawei; Yang, Zhongqiang; Liu, Dongsheng

    2015-03-01

    Amphiphilic DNA origami is prepared by dressing multiple hydrophobic molecules on a rectangular single layer DNA origami, which is then folded or coupled in sandwich-like structures with two outer DNA origami layer and one inner hydrophobic molecules layer. The preference to form different kinds of structures could be tailored by rational design of DNA origami. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Protection against the Metabolic Syndrome by Guar Gum-Derived Short-Chain Fatty Acids Depends on Peroxisome Proliferator-Activated Receptor. and Glucagon-Like Peptide-1

    NARCIS (Netherlands)

    den Besten, Gijs; Gerding, Albert; van Dijk, Theo H.; Ciapaite, Jolita; Bleeker, Aycha; van Eunen, Karen; Havinga, Rick; Groen, Albert K.; Reijngoud, Dirk-Jan; Bakker, Barbara M.

    2015-01-01

    The dietary fiber guar gum has beneficial effects on obesity, hyperglycemia and hypercholesterolemia in both humans and rodents. The major products of colonic fermentation of dietary fiber, the short-chain fatty acids (SCFAs), have been suggested to play an important role. Recently, we showed that

  10. Synthesis and performance of amphiphilic copolymers for blood cell separation.

    Science.gov (United States)

    Natori, Shizue Hayashi; Gomei, Yumiko; Higuchi, Akon

    2006-08-01

    Three types of amphiphilic copolymers using n-butylmethacrylate (BMA) as a hydrophobic monomer, and each of N,N'-dimethylacrylamide (DMA), N-acryloylmorpholine (AMO), and N-vinylpyrrolidone (VP) as hydrophilic comonomers were synthesized for coating filters used to remove leukocytes. The influence of the amphiphilic property of the resulting filters, which were composed of nonwoven fabrics coated with the above copolymers, on leukocyte removal and platelet permeation through the filters from whole blood was investigated. The platelet permeation ratio through hydrophobic noncoated filters was only 0.2%, because platelets in whole blood adhered easily to the hydrophobic filter material. However, filters coated with poly(AMO-co-BMA) of high AMO content showed a much higher platelet permeation ratio (nearly 90%). Further, the filters coated with poly(DMA-co-BMA) also showed high permeation ratios of platelets (more than 78%) over a broad range of DMA content in the copolymer. On the other hand, the coated filters showed slightly a higher permeation ratio of leukocytes than did the noncoated filters, resulting from the increase in hydrophilicity of the surface of the filters. Moreover, the coating of the amphiphilic copolymers on the surface of the nonwoven fabrics may have affected the pore size of the filters, affecting the permeation ratio of leukocytes more strongly than that of platelets. The coated filters effectively improved platelet permeation through the filters, with a slight increase in the permeation ratio of leukocytes.

  11. Amphiphiles Self-Assembly: Basic Concepts and Future Perspectives of Supramolecular Approaches

    Directory of Open Access Journals (Sweden)

    Domenico Lombardo

    2015-01-01

    Full Text Available Amphiphiles are synthetic or natural molecules with the ability to self-assemble into a wide variety of structures including micelles, vesicles, nanotubes, nanofibers, and lamellae. Self-assembly processes of amphiphiles have been widely used to mimic biological systems, such as assembly of lipids and proteins, while their integrated actions allow the performance of highly specific cellular functions which has paved a way for bottom-up bionanotechnology. While amphiphiles self-assembly has attracted considerable attention for decades due to their extensive applications in material science, drug and gene delivery, recent developments in nanoscience stimulated the combination of the simple approaches of amphiphile assembly with the advanced concept of supramolecular self-assembly for the development of more complex, hierarchical nanostructures. Introduction of stimulus responsive supramolecular amphiphile assembly-disassembly processes provides particularly novel approaches for impacting bionanotechnology applications. Leading examples of these novel self-assembly processes can be found, in fact, in biosystems where assemblies of different amphiphilic macrocomponents and their integrated actions allow the performance of highly specific biological functions. In this perspective, we summarize in this tutorial review the basic concept and recent research on self-assembly of traditional amphiphilic molecules (such as surfactants, amphiphile-like polymers, or lipids and more recent concepts of supramolecular amphiphiles assembly which have become increasingly important in emerging nanotechnology.

  12. Fine-mapping naturally occurring NY-ESO-1 antibody epitopes in melanoma patients' sera using short overlapping peptides and full-length recombinant protein.

    Science.gov (United States)

    Komatsu, Nobukazu; Jackson, Heather M; Chan, Kok-fei; Oveissi, Sara; Cebon, Jonathan; Itoh, Kyogo; Chen, Weisan

    2013-07-01

    The tumor antigen NY-ESO-1 is one of the most antigenic cancer-testis antigens, first identified by serologic analysis of a recombinant cDNA expression library (SEREX). NY-ESO-1 is expressed in different types of cancers including melanoma. NY-ESO-1-specific spontaneous humoral and cellular immune responses are detected in a large proportion of patients with advanced NY-ESO-1-expressing cancers. Therefore NY-ESO-1 is a good candidate antigen for immunotherapy. Although cellular immune responses to NY-ESO-1 are well characterized, much less is known about the humoral immune responses. In this study, we finely mapped linear antibody epitopes using sera from melanoma patients and shorter overlapping peptide sets. We have shown that melanoma patients' humoral immune systems responded to NY-ESO-1 differently in each individual with widely differing antibody specificity, intensity and antibody subtypes. This knowledge will help us further understand anti-tumor immunity and may also help us to monitor cancer progress and cancer vaccine efficacy in the future. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Efficient expression of a soluble lipid transfer protein (LTP) of Platanus orientalis using short peptide tags and structural comparison with the natural form.

    Science.gov (United States)

    Salari, Farhad; Vahedi, Fatemeh; Chamani, Jamshidkhan; Varasteh, Abdolreza; Ketabdar, Hanieh; Sankian, Mojtaba

    2015-01-01

    Successful recombinant allergen-based immunotherapy has drawn a great deal of attention to use recombinant allergens for new therapeutic and/or diagnostic strategies. The Escherichia coli expression system is frequently used to produce recombinant allergens; however, protein expression in E. coli often results in inclusion bodies. Here, we focused on the expression of two recombinant soluble forms of Pla or 3 using solubility-enhancing peptide tags, human immune deficiency virus type 1 transactivator of transcription core domain and poly-arginine-lysine: rTAT-Pla or 3 and rPoly-Arg-Lys-Pla or 3. Structural characteristics and IgE reactivity of purified recombinant proteins were compared with natural Pla or 3 (nPla or 3) isolated from Platanus orientalis using circular dichroism spectra, fluorescence spectroscopy, and immunoblotting. Likewise, intrinsic viscosity and Stokes radius of the natural and recombinant Pla or 3 allergens were determined to analyze structural compactness in aqueous media. The results indicate high-level solubility and efficient expression of the fusion proteins (rTAT-Pla or 3 and rPoly-Arg-Lys-Pla or 3) compared with the wild-type recombinant. Furthermore, the similar structural characteristics and IgE-binding activities of the fusion proteins to nPla or 3 provide a promising tool for allergy diagnosis and treatment. © 2014 International Union of Biochemistry and Molecular Biology, Inc.

  14. Amphiphilic Lipopeptide-Mediated Transport of Insulin and Cell Membrane Penetration Mechanism

    Directory of Open Access Journals (Sweden)

    Yu Zhang

    2015-12-01

    Full Text Available Arginine octamer (R8 and its derivatives were developed in this study for the enhanced mucosal permeation of insulin. R8 was substituted with different aminos, then modified with stearic acid (SA. We found that the SAR6EW-insulin complex had stronger intermolecular interactions and higher complex stability. The amphiphilic lipopeptide (SAR6EW was significantly more efficient for the permeation of insulin than R8 and R6EW both in vitro and in vivo. Interestingly, different cellular internalization mechanisms were observed for the complexes. When the effectiveness of the complexes in delivering insulin in vivo was examined, it was found that the SAR6EW-insulin complex provided a significant and sustained (six hours reduction in the blood glucose levels of diabetic rats. The improved absorption could be the comprehensive result of stronger intermolecular interactions, better enzymatic stability, altered internalization pathways, and increased transportation efficacy. In addition, no sign of toxicity was observed after consecutive administrations of SAR6EW. These results demonstrate that SAR6EW is a promising epithelium permeation enhancer for insulin and suggest that the chemical modification of cell-penetrating peptides is a feasible strategy to enhance their potential.

  15. Self-assembly of amphiphilic Janus dendrimers into mechanically robust supramolecular hydrogels for sustained drug release.

    Science.gov (United States)

    Nummelin, Sami; Liljeström, Ville; Saarikoski, Eve; Ropponen, Jarmo; Nykänen, Antti; Linko, Veikko; Seppälä, Jukka; Hirvonen, Jouni; Ikkala, Olli; Bimbo, Luis M; Kostiainen, Mauri A

    2015-10-05

    Compounds that can gelate aqueous solutions offer an intriguing toolbox to create functional hydrogel materials for biomedical applications. Amphiphilic Janus dendrimers with low molecular weights can readily form self-assembled fibers at very low mass proportion (0.2 wt %) to create supramolecular hydrogels (G'≫G'') with outstanding mechanical properties and storage modulus of G'>1000 Pa. The G' value and gel melting temperature can be tuned by modulating the position or number of hydrophobic alkyl chains in the dendrimer structure; thus enabling exquisite control over the mesoscale material properties in these molecular assemblies. The gels are formed within seconds by simple injection of ethanol-solvated dendrimers into an aqueous solution. Cryogenic TEM, small-angle X-ray scattering, and SEM were used to confirm the fibrous structure morphology of the gels. Furthermore, the gels can be efficiently loaded with different bioactive cargo, such as active enzymes, peptides, or small-molecule drugs, to be used for sustained release in drug delivery. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Strategic approaches to optimizing peptide ADME properties.

    Science.gov (United States)

    Di, Li

    2015-01-01

    Development of peptide drugs is challenging but also quite rewarding. Five blockbuster peptide drugs are currently on the market, and six new peptides received first marketing approval as new molecular entities in 2012. Although peptides only represent 2% of the drug market, the market is growing twice as quickly and might soon occupy a larger niche. Natural peptides typically have poor absorption, distribution, metabolism, and excretion (ADME) properties with rapid clearance, short half-life, low permeability, and sometimes low solubility. Strategies have been developed to improve peptide drugability through enhancing permeability, reducing proteolysis and renal clearance, and prolonging half-life. In vivo, in vitro, and in silico tools are available to evaluate ADME properties of peptides, and structural modification strategies are in place to improve peptide developability.

  17. H-shaped supra-amphiphiles based on a dynamic covalent bond.

    Science.gov (United States)

    Wang, Guangtong; Wang, Chao; Wang, Zhiqiang; Zhang, Xi

    2012-10-16

    The imine bond, a kind of dynamic covalent bond, is used to bind two bolaform amphiphiles together with spacers, yielding H-shaped supra-amphiphiles. Micellar aggregates formed by the self-assembly of the H-shaped supra-amphiphiles are observed. When pH is tuned down from basic to slightly acidic, the benzoic imine bond can be hydrolyzed, leading to the dissociation of H-shaped supra-amphiphiles. Moreover, H-shaped supra-amphiphiles have a lower critical micelle concentration than their building blocks, which is very helpful in enhancing the stability of the benzoic imine bond being hydrolyzed by acid. The surface tension isotherms of the H-shaped supra-amphiphiles with different spacers indicate their twisty conformation at a gas-water interface. The study of H-shaped supra-amphiphiles can enrich the family of amphiphiles, and moreover, the pH-responsiveness may make them apply to controlled or targetable drug delivery in a biological environment.

  18. Preparation of plasmonic vesicles from amphiphilic gold nanocrystals grafted with polymer brushes

    OpenAIRE

    Song, Jibin; Huang, Peng; Chen, Xiaoyuan

    2016-01-01

    Gold nanovesicles contain multiple nanocrystals within a polymeric coating. The strong plasmonic coupling between adjacent nanoparticles in their vesicular shell makes ultrasensitive biosensing and bioimaging possible. In our laboratory, multifunctional plasmonic vesicles are assembled from amphiphilic gold nanocrystals (such as gold nanoparticles and gold nanorods) coated with mixed hydrophilic and hydrophobic polymer brushes or amphiphilic diblock co-polymer brushes. To fulfill the differen...

  19. Amphiphile regulation of ion channel function by changes in the bilayer spring constant

    DEFF Research Database (Denmark)

    Lundbæk, Jens August; Koeppe, R.E.; Andersen, Oluf Sten

    2010-01-01

    effect of amphiphiles, at concentrations often used in biological research, on the bilayer elastic response to a change in the hydrophobic length of an embedded protein. The effects of structurally diverse amphiphiles can be described by changes in a phenomenological bilayer spring constant (H...

  20. Trapping of polycyclic aromatic hydrocarbons by amphiphilic cyclodextrin functionalized polypropylene nonwovens

    DEFF Research Database (Denmark)

    Lumholdt, Ludmilla; Nielsen, Ronnie Bo Højstrup; Larsen, Kim Lambertsen

    of the textile fibers. In this study we present the ability of amphiphilic CD coated polypropylene nonwovens to trap 8 different polycyclic aromatic hydrocarbons/endocrine disruptors from aqueous solutions thus demonstrating the potential of using the amphiphilic cyclodextrins for water purification....

  1. Supra-amphiphiles: a new bridge between colloidal science and supramolecular chemistry.

    Science.gov (United States)

    Kang, Yuetong; Liu, Kai; Zhang, Xi

    2014-06-03

    In addition to conventional amphiphiles, an emerging research area is supra-amphiphiles, which are constructed on the basis of noncovalent interactions and dynamic covalent bonds. In this feature article, we have provided a general introduction to the concept, design principles, and topologies of supra-amphiphiles, starting from some rationally tailored building blocks. In addition, we highlight some progress in the functional assembly of supra-amphiphiles, such as responsive nanoscale carriers, antibacterial and antitumor agents, fluorescent-based chemical sensors, and enzyme mimics. The supra-amphiphile is a new bridge between colloidal science and supramolecular chemistry, and it is a field where we can make full use of our imaginative power.

  2. Exploring single chain amphiphile self-assembly and their possible roles in light transduction

    DEFF Research Database (Denmark)

    Monnard, Pierre-Alain

    2011-01-01

    amphiphiles on the early Earth seems reasonably well-documented either by exo-terrestrial delivery or endogeneous syntheses, a fact that singles them out as potential building blocks of primitive membranes. These studies have highlighted two important aspects of the self-assembly of single chain amphiphiles......Self-assembled structures of single-chain amphiphiles have been used as hosts for biochemical, and chemical reactions. Their use as models for protocells (i.e., precursors to the first biological cells) has been extensively researched by various groups because the availability of single chain...... source studied to date can supply one single type of amphiphile at concentrations conducive to self-assembly. Mixtures of single-chain amphiphiles were therefore proposed to better model primitive membranes and potentially enhance their structural integrity1-3. Recently, we have established that complex...

  3. Vesicles from Amphiphilic Dumbbells and Janus Dendrimers: Bioinspired Self-Assembled Structures for Biomedical Applications

    Directory of Open Access Journals (Sweden)

    Soraya Taabache

    2017-07-01

    Full Text Available The current review focuses on vesicles obtained from the self-assembly of two types of dendritic macromolecules, namely amphiphilic Janus dendrimers (forming dendrimersomes and amphiphilic dumbbells. In the first part, we will present some synthetic strategies and the various building blocks that can be used to obtain dendritic-based macromolecules, thereby showing their structural versatility. We put our focus on amphiphilic Janus dendrimers and amphiphilic dumbbells that form vesicles in water but we also encompass vesicles formed thereof in organic solvents. The second part of this review deals with the production methods of these vesicles at the nanoscale but also at the microscale. Furthermore, the influence of various parameters (intrinsic to the amphiphilic JD and extrinsic—from the environment on the type of vesicle formed will be discussed. In the third part, we will review the numerous biomedical applications of these vesicles of nano- or micron-size.

  4. Short communication: Glucagon-like peptide-2 and coccidiosis alter tight junction gene expression in the gastrointestinal tract of dairy calves.

    Science.gov (United States)

    Walker, M P; Evock-Clover, C M; Elsasser, T H; Connor, E E

    2015-05-01

    Tight junction (TJ) proteins are integral factors involved in gut barrier function, and therapy with glucagon-like peptide-2 (GLP-2) enhances gut integrity. Our aim was to assess effects of GLP-2 treatment on mRNA expression of 8 TJ complex proteins in the intestine of dairy calves not infected or infected with Eimeria bovis at 11±3d of age. Mucosal epithelium from jejunum, ileum, and cecum was collected at slaughter from Holstein bull calves assigned to 4 groups: noninfected, buffer-treated (n=5); noninfected, GLP-2 treated (n=4); E. bovis-infected, buffer-treated (n=5); and E. bovis-infected, GLP-2-treated (n=4). Infected calves were orally dosed with 100,000 to 200,000 sporulated E. bovis oocysts on d 0; GLP-2-treated calves received 50 µg of GLP-2/kg of body weight subcutaneously twice daily for 10d beginning on d 18; and buffer-treated calves received an equal injection volume of 0.01 M Na bicarbonate buffer. All calves were killed on d 28. The mRNA expression of coxsackie and adenovirus receptor (CXADR), claudins 1, 2, and 4 (CLDN1, CLDN2, and CLDN4), F11 receptor (F11R), junction adhesion molecule 2 (JAM2), occludin (OCLN), and tight junction protein ZO-1 (TJP1) was determined by real-time quantitative PCR. In jejunum and ileum, an interaction of E. bovis infection and GLP-2 treatment on gene expression was noted. In jejunum of noninfected calves, GLP-2 increased CXADR, CLDN2, OCLN, and TJP1 mRNA expression but had no effect on mRNA expression in infected calves. Treatment with GLP-2 also increased tight junction protein ZO-1 protein expression in jejunum of noninfected calves as determined by immunohistochemistry. In ileum, E. bovis decreased expression of JAM2, OCLN, and TJP1 in buffer-treated calves, and GLP-2 increased TJP1 expression in infected calves. In cecum, E. bovis infection reduced expression of CXADR, CLDN4, F11R, and OCLN, and GLP-2 therapy increased expression of CLDN4, F11R, OCLN, and TJP1. Results are consistent with studies in

  5. Nucleobase-mediated, photocatalytic production of amphiphiles to promote the self-assembly of a simple self-replicating protocell.

    Science.gov (United States)

    Monnard, Pierre-Alain; Maurer, Sarah, E.; Albertsen, Anders, N.; Boncella, James, M.; Cape, Jonathan, L.

    replaced by a single nucleobase, 8-oxoguanine, which is tethered to one bipyridine ligand of the metal center. We report here the following major steps towards this chemical protocell: 1) the spontaneous formation of chemical structures consisting of decanoic acid, its precursor, and the simplified NA-ruthenium complexes. 2) the metabolism mediation by a nucleobase to effectively promote the photochemical amphiphile synthesis. 3) the demonstration of reaction selectivity dependent on the nature of the information molecule since only one specific nucleobase that has the required redox potential allows the metabolism to function. Finally, 4) the photochemical formation of amphiphiles can occur efficiently within a preformed membrane, i.e., the protocell compartment. The next step is the integration of short nucleic acid oligomers as opposed to a single nucleobase as the information material to study their photocatalytic activity mediation and polymerization.

  6. High affinity γPNA sandwich hybridization assay for rapid detection of short nucleic acid targets with single mismatch discrimination.

    Science.gov (United States)

    Goldman, Johnathan M; Zhang, Li Ang; Manna, Arunava; Armitage, Bruce A; Ly, Danith H; Schneider, James W

    2013-07-08

    Hybridization analysis of short DNA and RNA targets presents many challenges for detection. The commonly employed sandwich hybridization approach cannot be implemented for these short targets due to insufficient probe-target binding strengths for unmodified DNA probes. Here, we present a method capable of rapid and stable sandwich hybridization detection for 22 nucleotide DNA and RNA targets. Stable hybridization is achieved using an n-alkylated, polyethylene glycol γ-carbon modified peptide nucleic acid (γPNA) amphiphile. The γPNA's exceptionally high affinity enables stable hybridization of a second DNA-based probe to the remaining bases of the short target. Upon hybridization of both probes, an electrophoretic mobility shift is measured via interaction of the n-alkane modification on the γPNA with capillary electrophoresis running buffer containing nonionic surfactant micelles. We find that sandwich hybridization of both probes is stable under multiple binding configurations and demonstrate single base mismatch discrimination. The binding strength of both probes is also stabilized via coaxial stacking on adjacent hybridization to targets. We conclude with a discussion on the implementation of the proposed sandwich hybridization assay as a high-throughput microRNA detection method.

  7. Nanocellulose-based biosensors: design, preparation, and activity of peptide-linked cotton cellulose nanocrystals having fluorimetric and colorimetric elastase detection sensitivity

    Science.gov (United States)

    Nanocrystalline cellulose is an amphiphilic, high surface area material that can be easily functionalized and is biocom-patible and eco-friendly. It has been used singularly and in combination with other nanomaterials to optimize biosensor design. The attachment of peptides and proteins to nanocryst...

  8. Amphiphilic photosensitive dextran-g-poly(o-nitrobenzyl acrylate) glycopolymers.

    Science.gov (United States)

    Soliman, Soliman Mehawed Abdellatif; Colombeau, Ludovic; Nouvel, Cécile; Babin, Jérôme; Six, Jean-Luc

    2016-01-20

    Among all photosensitive monomers reported in the literature, o-nitrobenzyl acrylate (NBA) was selected in this present study. Two strategies were compared to produce azido-terminated poly(o-nitrobenzyl acrylate) (PNBA) using controlled Single Electron Transfer-Living Radical Polymerization (SET-LRP). In a parallel way, dextran (Dex) was modified by the introduction of several alkynyl-terminated hydrophobic chains. Finally, an Huisgen-type Copper (I)-catalyzed Azide-Alkyne Cycloaddition (CuAAC) click-chemistry was carried out to produce amphiphilic Dex-g-PNBA glycopolymers with different number and length of PNBA grafts. 2D DOSY (1)H NMR was used to prove the formation of such glycopolymers. Preliminary study on Dex-g-PNBA self-assembly was done by measuring the critical water content (CWC) above which Dex-g-PNBA started to auto-organize themselves to produce nano-objects. Finally, under UV irradiation, PNBA grafts turn into poly(acrylic acid) ones giving light-sensitive properties to such amphiphilic Dex-g-PNBA. Such properties were evaluated and compared with those of PNBA. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Amphiphilic Silane Modified Multifunctional Nanoparticles for Magnetically Targeted Photodynamic Therapy.

    Science.gov (United States)

    Sun, Xueke; Dong, Biao; Xu, Hongwei; Xu, Shihan; Zhang, Xinran; Lin, Yanxia; Xu, Lin; Bai, Xue; Zhang, Shuang; Song, Hongwei

    2017-04-05

    Efficient targeting is a major challenge in practical photodynamic therapy (PDT). Though the "enhanced permeability and retention" (EPR) effect is a widely used tumor targeting method, magnetic targeting strategy is more promising considering the issue of high targeting efficiency and reducing concentration-dependent toxicity. Herein, magnetic targeting and highly effective Fe 3 O 4 @Ce6/C6@silane NPs are reported as a class of precisely controlled photosensitizers (PS) for PDT. On the basis of the amphiphilic silane encapsulation, PS chlorin e6 (Ce6) and Coumarin 6 (C6) as well as Fe 3 O 4 NPs were coloaded into the inside hydrophobic environment of amphiphilic silane, forming a theranostic agent for dual-mode imaging guided and magnetic targeting enhanced in vivo PDT agent. To solve the problem of over-irradiation, the coloaded design of C6 and Ce6 molecules can afford the real time PDT monitoring by ratio emissions with same excitation wavelength. When Fe 3 O 4 @Ce6/C6@silane and Ce6/C6@silane NPs are compared in in vitro and in vivo experiments, the introduction of Fe 3 O 4 in the composite does not affect the PDT efficiency, whereas, in contrast, it brings MRI imaging and magnetic targeting functions. Fe 3 O 4 @Ce6/C6@silane injection followed with magnetic field (MF) and light irradiation is important in generating an effective PDT process, showing great potential in tumor therapy.

  10. Protection against the Metabolic Syndrome by Guar Gum-Derived Short-Chain Fatty Acids Depends on Peroxisome Proliferator-Activated Receptor γ and Glucagon-Like Peptide-1.

    Science.gov (United States)

    den Besten, Gijs; Gerding, Albert; van Dijk, Theo H; Ciapaite, Jolita; Bleeker, Aycha; van Eunen, Karen; Havinga, Rick; Groen, Albert K; Reijngoud, Dirk-Jan; Bakker, Barbara M

    2015-01-01

    The dietary fiber guar gum has beneficial effects on obesity, hyperglycemia and hypercholesterolemia in both humans and rodents. The major products of colonic fermentation of dietary fiber, the short-chain fatty acids (SCFAs), have been suggested to play an important role. Recently, we showed that SCFAs protect against the metabolic syndrome via a signaling cascade that involves peroxisome proliferator-activated receptor (PPAR) γ repression and AMP-activated protein kinase (AMPK) activation. In this study we investigated the molecular mechanism via which the dietary fiber guar gum protects against the metabolic syndrome. C57Bl/6J mice were fed a high-fat diet supplemented with 0% or 10% of the fiber guar gum for 12 weeks and effects on lipid and glucose metabolism were studied. We demonstrate that, like SCFAs, also guar gum protects against high-fat diet-induced metabolic abnormalities by PPARγ repression, subsequently increasing mitochondrial uncoupling protein 2 expression and AMP/ATP ratio, leading to the activation of AMPK and culminating in enhanced oxidative metabolism in both liver and adipose tissue. Moreover, guar gum markedly increased peripheral glucose clearance, possibly mediated by the SCFA-induced colonic hormone glucagon-like peptide-1. Overall, this study provides novel molecular insights into the beneficial effects of guar gum on the metabolic syndrome and strengthens the potential role of guar gum as a dietary-fiber intervention.

  11. Protection against the Metabolic Syndrome by Guar Gum-Derived Short-Chain Fatty Acids Depends on Peroxisome Proliferator-Activated Receptor γ and Glucagon-Like Peptide-1.

    Directory of Open Access Journals (Sweden)

    Gijs den Besten

    Full Text Available The dietary fiber guar gum has beneficial effects on obesity, hyperglycemia and hypercholesterolemia in both humans and rodents. The major products of colonic fermentation of dietary fiber, the short-chain fatty acids (SCFAs, have been suggested to play an important role. Recently, we showed that SCFAs protect against the metabolic syndrome via a signaling cascade that involves peroxisome proliferator-activated receptor (PPAR γ repression and AMP-activated protein kinase (AMPK activation. In this study we investigated the molecular mechanism via which the dietary fiber guar gum protects against the metabolic syndrome. C57Bl/6J mice were fed a high-fat diet supplemented with 0% or 10% of the fiber guar gum for 12 weeks and effects on lipid and glucose metabolism were studied. We demonstrate that, like SCFAs, also guar gum protects against high-fat diet-induced metabolic abnormalities by PPARγ repression, subsequently increasing mitochondrial uncoupling protein 2 expression and AMP/ATP ratio, leading to the activation of AMPK and culminating in enhanced oxidative metabolism in both liver and adipose tissue. Moreover, guar gum markedly increased peripheral glucose clearance, possibly mediated by the SCFA-induced colonic hormone glucagon-like peptide-1. Overall, this study provides novel molecular insights into the beneficial effects of guar gum on the metabolic syndrome and strengthens the potential role of guar gum as a dietary-fiber intervention.

  12. Cationic Amphiphilic Tris-Cyclometalated Iridium(III) Complexes Induce Cancer Cell Death via Interaction with Ca2+-Calmodulin Complex.

    Science.gov (United States)

    Hisamatsu, Yosuke; Suzuki, Nozomi; Masum, Abdullah-Al; Shibuya, Ai; Abe, Ryo; Sato, Akira; Tanuma, Sei-Ichi; Aoki, Shin

    2017-02-15

    In our previous paper, we reported on the preparation of some cationic amphiphilic Ir complexes (2c, 2d) containing KKGG peptides that induce and detect cell death of Jurkat cells. Mechanistic studies suggest that 2c interacts with anionic molecules and/or membrane receptors on the cell surface to trigger an intracellular Ca 2+ response, resulting in the induction of cell death, accompanied by membrane disruption. We have continued the studies of cell death of Jurkat cells induced by 2c and found that xestospongin C, a selective inhibitor of an inositol 1,4,5-trisphosphate receptor located on the endoplasmic reticulum (ER), reduces the cytotoxicity of 2c, suggesting that 2c triggers the release of Ca 2+ from the ER, leading to an increase in the concentration of cytosolic Ca 2+ , thus inducing cell death. Moreover, we synthesized a series of new amphiphilic cationic Ir complexes 5a-c containing photoreactive 3-trifluoromethyl-3-phenyldiazirine (TFPD) groups, in an attempt to identify the target molecules of 2c. Interestingly, it was discovered that a TFPD group functions as a triplet quencher of Ir complexes. It was also found that 5b is useful as a turn-on phosphorescent probe of acidic proteins such as bovine serum albumin (BSA) (pI = 4.7) and their complexation was confirmed by luminescence titrations and SDS-PAGE of photochemical products between them. These successful results allowed us to carry out photoaffinity labeling of the target biomolecules of 5b (2c and analogues thereof) in Jurkat cells. A proteomic analysis of the products obtained by the photoirradiation of 5b with Jurkat cells suggests that the Ca 2+ -binding protein "calmodulin (CaM)" is one of target proteins of the Ir complexes. Indeed, 5b was found to interact with the Ca 2+ -CaM complex, as evidenced by luminescence titrations and the results of photochemical reactions of 5b with CaM in the presence of Ca 2+ (SDS-PAGE). A plausible mechanism for cell death induced by a cationic amphiphilic Ir

  13. High Specific Selectivity and Membrane-Active Mechanism of Synthetic Cationic Hybrid Antimicrobial Peptides Based on the Peptide FV7.

    Science.gov (United States)

    Tan, Tingting; Wu, Di; Li, Weizhong; Zheng, Xin; Li, Weifen; Shan, Anshan

    2017-02-06

    Hybrid peptides integrating different functional domains of peptides have many advantages, such as remarkable antimicrobial activity, lower hemolysis and ideal cell selectivity, compared with natural antimicrobial peptides. FV7 (FRIRVRV-NH₂), a consensus amphiphilic sequence was identified as being analogous to host defense peptides. In this study, we designed a series of hybrid peptides FV7-LL-37 (17-29) (FV-LL), FV7-magainin 2 (9-21) (FV-MA) and FV7-cecropin A (1-8) (FV-CE) by combining the FV7 sequence with the small functional sequences LL-37 (17-29) (LL), magainin 2 (9-21) (MA) and cecropin A (1-8) (CE) which all come from well-described natural peptides. The results demonstrated that the synthetic hybrid peptides, in particular FV-LL, had potent antibacterial activities over a wide range of Gram-negative and Gram-positive bacteria with lower hemolytic activity than other peptides. Furthermore, fluorescent spectroscopy indicated that the hybrid peptide FV-LL exhibited marked membrane destruction by inducing outer and inner bacterial membrane permeabilization, while scanning electron microscopy (SEM) and transmission electron microscopy (TEM) demonstrated that FV-LL damaged membrane integrity by disrupting the bacterial membrane. Inhibiting biofilm formation assays also showed that FV-LL had similar anti-biofilm activity compared with the functional peptide sequence FV7. Synthetic cationic hybrid peptides based on FV7 could provide new models for combining different functional domains and demonstrate effective avenues to screen for novel antimicrobial agents.

  14. Asymmetric and symmetric bolaform supra-amphiphiles: formation of imine bond influenced by aggregation.

    Science.gov (United States)

    Wang, Guangtong; Wu, Guanglu; Wang, Zhiqiang; Zhang, Xi

    2014-02-18

    A series of bolaform supra-amphilphiles with different symmetries were fabricated through dynamic benzoic imine bond formation. The pH dependence of imine formations of these supra-amphiphiles were characterazied. We found that the extent of the imine formation of these supra-amphiphies were different. The supra-amphiphiles with a poorer symmetry always exhibited a lower imine formation at a given pH. Therefore, the varied extent of imine bond formation indicate the different aggregations of these supra-amphilphiles, which are controlled by the molecular symmetry of the supra-amphiphiles.

  15. Stable Vesicles Composed of Mono- or Dicarboxylic Fatty Acids and Trimethylammonium Amphiphiles

    DEFF Research Database (Denmark)

    Caschera, Filippo; Bernardino de la Serna, Jorge; Löffler, Philipp M. G.

    2011-01-01

    shown to be more stable than those formed by pure fatty acids. Those containing bola-amphiphile even showed encapsulation of a small hydrophilic solute (8-hydroxypyrene-1,3,6-trisulfonic-acid) suggesting a denser packing of the amphiphiles. Compression and kinetics analysis of monolayers composed...... of these amphiphiles mixtures at the air/water interface suggest that the stabilization of the structures can be attributed to two main interactions between headgroups, predominantly the formation of hydrogen bonds between protonated and deprotonated acids and then the additional electrostatic interactions between...

  16. (CryoTransmission Electron Microscopy of Phospholipid Model Membranes Interacting with Amphiphilic and Polyphilic Molecules

    Directory of Open Access Journals (Sweden)

    Annette Meister

    2017-10-01

    Full Text Available Lipid membranes can incorporate amphiphilic or polyphilic molecules leading to specific functionalities and to adaptable properties of the lipid bilayer host. The insertion of guest molecules into membranes frequently induces changes in the shape of the lipid matrix that can be visualized by transmission electron microscopy (TEM techniques. Here, we review the use of stained and vitrified specimens in (cryoTEM to characterize the morphology of amphiphilic and polyphilic molecules upon insertion into phospholipid model membranes. Special emphasis is placed on the impact of novel synthetic amphiphilic and polyphilic bolalipids and polymers on membrane integrity and shape stability.

  17. Amphiphile replacement on carbon nanotube surfaces: Effect of aromatic groups on the interaction strength

    Energy Technology Data Exchange (ETDEWEB)

    Bluemmel, Pascal; Setaro, Antonio; Reich, Stephanie [Institut fuer Experimentalphysik, Freie Universitaet Berlin, Arnimallee 14, 14195 Berlin (Germany); Popeney, Chris S.; Trappmann, Britta; Haag, Rainer [Institut fuer Chemie und Biochemie, Freie Universitaet Berlin, Takustrasse 3, 14195 Berlin (Germany)

    2011-11-15

    Carbon nanotubes (CNTs) were solubilized using akyl/polyglycerol amphiphiles. Similar cosurfactants, bearing different aromatic moieties between head and tail, were added to these samples. The interaction strength between these amphiphiles and CNTs changes depending on the inserted aromatic moieties. The insertion of a phenyl ring allows the amphiphile to replace the starting one indicating a higher interaction strength, while the insertion of a triazol pentagon does not, suggesting that the interaction strength is lower. The replacement was monitored via PLE mapping. (Copyright copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  18. Synthesis and Application of a New Amphiphilic Antioxidant.

    Science.gov (United States)

    Soliman, Hanaa M; Arafat, Shaker M; Basuny, Amany M; Shattory, Y El-

    2017-11-01

    A new amphiphilic antioxidant (tannyl stearate) derived from reaction of tannic acid with stearic acid was synthesized in order to improve tannic acid solubility in lipid materials. This reaction gives many products having different degree of esterification (tannyl mono, di, tri, tetra, penta, hexa, hepta……stearate) which were separated using silica gel column chromatography and tentative identification was carried out using thin layer chromatography (TLC). The intrinsic viscosities (η) were used to differentiate between the different molecular weight of the produced esters 1) . Tannyl penta stearate is assumed to be the most suitable amphiphilic antioxidant derivative, where those derivatives with less degree of esterification would be less soluble in fat, and those of higher degree of esterification would exhaust more hydroxyl group that cause decreases of antioxidant activity. The structure of tannyl penta stearate was approved depending on its chemical analysis and spectral data (IR, H 1 NMR,). The emulsification power of tannyl penta stearate was then determined according to method described by El-Sukkary et al. 2) , in order to prove its amphiphilic property. Then tannyl penta stearate was tested for its antioxidant and radical scavenging activities in three different manners, those are, lipid oxidation in sunflower oil using Rancimat, (DPPH) free radical scavenging and total antioxidant activity. {Pure tannic acid (T), butylhydroxyanisol (BHA) and butylhydroxytoluene (BHT) were used as reference antioxidant radical saving compounds}. Then tannyl penta stearate was added to sunflower oil, frying process was carried out and all physicochemical parameters of the oil were considered, and compared to other reference antioxidant in order to study the effect of this new antioxidant toward oil stability. Acute oral toxicity of the tannyl penta stearate was carried out using albino mice of 21-25 g body weight to determine its safety according to the method

  19. Surface modification using peptide functionalized bilayers

    Science.gov (United States)

    Stroumpoulis, Dimitrios

    Engineering materials that are capable of supporting cell and tissue growth is a challenging task that involves identifying and incorporating biological signals into the material surfaces or scaffolds. One approach towards bioactivity in materials is to mimic the function of the extracellular matrix (ECM) by displaying adhesion promoting oligopeptides. Supported planar bilayers (SPB) are a good platform to study molecular interactions at interfaces, since transmembrane proteins and peptides can be incorporated in a biologically relevant environment with precise control over their concentration and presentation. SPBs can be formed on flat surfaces using the Langmuir-Blodgett (LB) technique or alternatively from vesicle solutions. The fusion of vesicles with solid substrates offers simplicity and enhanced bilayer deposition rates over the LB method, whereas it can also be used with convex and enclosed surfaces. Ellipsometry and a mass transport model were used to investigate the kinetics of SPB formation on silicon dioxide surfaces from 100 nm diameter 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) vesicles. For the range of concentrations studied, 0.025 to 0.380 mg/ml, a monotonic increase in the ellipsometric signal with time was observed until saturation and the adsorption rate constant was calculated. Further, a Monte Carlo model was used to simulate the SPB formation process and the computational results were successfully fit to the experimental data. Lipid vesicles displaying RGD peptide amphiphiles were fused onto glass coverslips to control the ability of these surfaces to support cell adhesion and growth. Cell adhesion was prevented on phosphatidylcholine bilayers in the absence of RGD, whereas cells adhered and spread in the presence of accessible RGD amphiphiles. This specific interaction between cells and RGD peptides was further explored in a concentration dependent fashion by creating a surface composition array using a microfluidic device. For the

  20. Formation of nanoscale networks: selectively swelling amphiphilic block copolymers with CO2-expanded liquids.

    Science.gov (United States)

    Gong, Jianliang; Zhang, Aijuan; Bai, Hua; Zhang, Qingkun; Du, Can; Li, Lei; Hong, Yanzhen; Li, Jun

    2013-02-07

    Polymeric films with nanoscale networks were prepared by selectively swelling an amphiphilic diblock copolymer, polystyrene-block-poly(4-vinylpyridine) (PS-b-P4VP), with the CO(2)-expanded liquid (CXL), CO(2)-methanol. The phase behavior of the CO(2)-methanol system was investigated by both theoretical calculation and experiments, revealing that methanol can be expanded by CO(2), forming homogeneous CXL under the experimental conditions. When treated with the CO(2)-methanol system, the spin cast compact PS-b-P4VP film was transformed into a network with interconnected pores, in a pressure range of 12-20 MPa and a temperature range of 45-60 °C. The formation mechanism of the network, involving plasticization of PS and selective swelling of P4VP, was proposed. Because the diblock copolymer diffusion process is controlled by the activated hopping of individual block copolymer chains with the thermodynamic barrier for moving PVP segments from one to another, the formation of the network structures is achieved in a short time scale and shows "thermodynamically restricted" character. Furthermore, the resulting polymer networks were employed as templates, for the preparation of polypyrrole networks, by an electrochemical polymerization process. The prepared porous polypyrrole film was used to fabricate a chemoresistor-type gas sensor which showed high sensitivity towards ammonia.

  1. Poly(phenylene ether Based Amphiphilic Block Copolymers

    Directory of Open Access Journals (Sweden)

    Edward N. Peters

    2017-09-01

    Full Text Available Polyphenylene ether (PPE telechelic macromonomers are unique hydrophobic polyols which have been used to prepare amphiphilic block copolymers. Various polymer compositions have been synthesized with hydrophilic blocks. Their macromolecular nature affords a range of structures including random, alternating, and di- and triblock copolymers. New macromolecular architectures can offer tailored property profiles for optimum performance. Besides reducing moisture uptake and making the polymer surface more hydrophobic, the PPE hydrophobic segment has good compatibility with polystyrene (polystyrene-philic. In general, the PPE contributes to the toughness, strength, and thermal performance. Hydrophilic segments go beyond their affinity for water. Improvements in the interfacial adhesion between polymers and polar substrates via hydrogen bonding and good compatibility with polyesters (polyester-philic have been exhibited. The heterogeneity of domains in these PPE based block copolymer offers important contributions to diverse applications.

  2. Structure and reactivity in amphiphile-water micelles

    International Nuclear Information System (INIS)

    Chevalier, Yves

    1985-01-01

    Following a review of the general properties of micelles, this report contains two parts: - A structural study of octylphosphate micelles. Important structural changes have been evidenced by mean of small angle neutron scattering as the electrical charge of the interface is varied. The NMR relaxation study of the conformation of the hydrocarbon chains has shown that the micellar core is disordered in contrast with the interface which is rather structured. The diffusion motions in the interface and the segmental motions of the chains are fast. - Studies on the reactivity in micelles have been carried out. A large micellar effect on the complexation of transition ions by amphiphilic ligands is evidenced. The problem of solute localization in micelles is developed with few examples. (author) [fr

  3. Interaction of amphiphilic drugs with human and bovine serum albumins.

    Science.gov (United States)

    Khan, Abbul Bashar; Khan, Javed Masood; Ali, Mohd Sajid; Khan, Rizwan Hasan; Kabir-Ud-Din

    2012-11-01

    To know the interaction of amphiphilic drugs nortriptyline hydrochloride (NOT) and promazine hydrochloride (PMZ) with serum albumins (i.e., human serum albumin (HSA) and bovine serum albumin (BSA)), techniques of UV-visible, fluorescence, and circular dichroism (CD) spectroscopies are used. The binding affinity is more in case of PMZ with both the serum albumins. The quenching rate constant (k(q)) values suggest a static quenching process for all the drug-serum albumin interactions. The UV-visible results show that the change in protein conformation of PMZ-serum albumin interactions are more prominent as compared to NOT-serum albumin interactions. The CD results also explain the conformational changes in the serum albumins on binding with the drugs. The increment in %α-helical structure is slightly more for drug-BSA complexes as compared to drug-HSA complexes. Copyright © 2012 Elsevier B.V. All rights reserved.

  4. Synthesis and properties of amphiphilic hyperbranched polyethers as pigment dispersant

    Science.gov (United States)

    Xu, Q.; Zhou, Y. J.; Long, S. J.; Liu, Y. G.; Li, J. H.

    2018-01-01

    Hyperbranched polymers possess prominent properties such as low viscosity, good solubility, high rheological property, environmental non-toxic, and so on, which have potential applications in coatings. In this study, the amphiphilic hyperbranched polyethers (AHPs) consisting of hydrophobic hyperbranched polyethers core and hydrophilic poly (ethylene glycol) arms with different degree of branching (DB) under various reaction temperatures was prepared by the cation ring-opening polymerization. Their structures were characterized by IR, 13CNMR and GPC. Their dispersion properties for pigment particles were investigated. The AHP47 with 0.47 DB was found to have good dispersion properties for Yellow HGR. This work would provide experimental data and theoretical foundation for the application of hyperbranched polyethers in environmental protection coating.

  5. Adsorption of sub-micron amphiphilic dumbbells to fluid interfaces.

    Science.gov (United States)

    Isa, Lucio; Samudrala, Niveditha; Dufresne, Eric R

    2014-05-13

    We investigate the adsorption of submicrometer bulk-synthesized polymer dumbbells to oil-water interfaces using freeze-fracture, shadow-casting (FreSCa) cryo-scanning electron microscopy. We find that the dumbbells are amphiphilic and adsorb to the interface with a preferred orientation. Most particles adsorb in a tilted configuration, with the polar and apolar lobes intersecting the interface and pointing toward the water and oil, respectively. Some particles adsorb with only one lobe attached to the interface. Moreover, we find that each lobe has a preferred angle of contact with the interface, identical in all observed configurations. A simple geometrical calculation using these contact angles accurately predicts the dominant configuration of particles at the interface. This calculation provides insight into how the shape and composition of dumbbells can be tuned to stand upright and pack efficiently on curved interfaces.

  6. Antifungal amphiphilic aminoglycoside K20: bioactivities and mechanism of action

    Directory of Open Access Journals (Sweden)

    Sanjib K. Shrestha

    2014-12-01

    Full Text Available K20 is a novel amphiphilic antifungal aminoglycoside that is synthetically derived from the antibiotic kanamycin A. Reported here are investigations of K20’s antimicrobial activities, cytotoxicity, and fungicidal mechanism of action. In vitro growth inhibitory activities against a variety of human and plant pathogenic yeasts, filamentous fungi, and bacteria were determined using microbroth dilution assays and time-kill curve analyses, and hemolytic and animal cell cytotoxic activities were determined. Effects on Cryptococcus neoformans H-99 infectivity were determined with a preventive murine lung infection model. The antifungal mechanism of action was studied using intact fungal cells, yeast lipid mutants, and small unilamellar lipid vesicles. K20 exhibited broad-spectrum in vitro antifungal activities but not antibacterial activities. Pulmonary, single dose-administration of K20 reduced C. neoformans lung infection rates 4-fold compared to controls. Hemolysis and half-maximal cytotoxicities of mammalian cells occurred at concentrations that were 10 to 32-fold higher than fungicidal MICs. With fluorescein isothiocyanate, 20 to 25 mg/L K20 caused staining of >95% of C. neoformans and Fusarium graminearum cells and at 31.3 mg/L caused rapid leakage (30 to 80% in 15 min of calcein from preloaded small unilamellar lipid vesicles. K20 appears to be a broad-spectrum fungicide, capable of reducing the infectivity of C. neoformans, and exhibits low hemolytic activity and mammalian cell toxicity. It perturbs the plasma membrane by mechanisms that are lipid modulated. K20 is a novel amphiphilic aminoglycoside amenable to scalable production and a potential lead antifungal for therapeutic and crop protection applications.

  7. Aminoglycoside-derived amphiphilic nanoparticles for molecular delivery.

    Science.gov (United States)

    Miryala, Bhavani; Godeshala, Sudhakar; Grandhi, Taraka Sai Pavan; Christensen, Matthew D; Tian, Yanqing; Rege, Kaushal

    2016-10-01

    The development of effective drug carriers can lead to improved outcomes in a variety of disease conditions. Aminoglycosides have been used as antibacterial therapeutics, and are attractive as monomers for the development of polymeric materials in various applications. Here, we describe the development of novel aminoglycoside-derived amphiphilic nanoparticles for drug delivery, with an eye towards ablation of cancer cells. The aminoglycoside paromomycin was first cross-linked with resorcinol diglycidyl ether leading to the formation of a poly (amino ether), PAE. PAE molecules were further derivatized with methoxy-terminated poly(ethylene glycol) or mPEG resulting in the formation of mPEG-PAE polymer, which self-assembled to form nanoparticles. Formation of the mPEG-PAE amphiphile was characterized using (1)H NMR, (13)C NMR, gel permeation chromatography (GPC) and FTIR spectroscopy. Self-assembly of the polymer into nanoparticles was characterized using dynamic light scattering, zeta potential analyses, atomic force microscopy (AFM) and the pyrene fluorescence assay. mPEG-PAE nanoparticles were able to carry significant amounts of doxorubicin (DOX), presumably by means of hydrophobic interactions between the drug and the core. Cell-based studies indicated that mPEG-PAE nanoparticles, loaded with doxorubicin, were able to induce significant loss in viabilities of PC3 human prostate cancer, MDA-MB-231 human breast cancer, and MB49 murine bladder cancer cells; empty nanoparticles resulted in negligible losses of cell viability under the conditions investigated. Taken together, our results indicate that the mPEG-PAE nanoparticle platform is attractive for drug delivery in different applications, including cancer. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Molecular Design, Structures, and Activity of Antimicrobial Peptide-Mimetic Polymers

    Science.gov (United States)

    Takahashi, Haruko; Palermo, Edmund F.; Yasuhara, Kazuma; Caputo, Gregory A.

    2014-01-01

    There is an urgent need for new antibiotics which are effective against drug-resistant bacteria without contributing to resistance development. We have designed and developed antimicrobial copolymers with cationic amphiphilic structures based on the mimicry of naturally occurring antimicrobial peptides. These copolymers exhibit potent antimicrobial activity against a broad spectrum of bacteria including methicillin-resistant Staphylococcus aureus with no adverse hemolytic activity. Notably, these polymers also did not result in any measurable resistance development in E. coli. The peptide-mimetic design principle offers significant flexibility and diversity in the creation of new antimicrobial materials and their potential biomedical applications. PMID:23832766

  9. Conformational Aspects of High Content Packing of Antimicrobial Peptides in Polymer Microgels

    DEFF Research Database (Denmark)

    Singh, Shalini; Datta, Aritreyee; Borro, Bruno C

    2017-01-01

    , consequences of peptide loading and release for membrane interactions and antimicrobial effects were investigated. In doing so, poly(ethyl acrylate-co-methacrylic acid) microgels were found to incorporate the cationic AMPs EFK17a (EFKRIVQRIKDFLRNLV) and its partially d-amino acid-substituted variant EFK17da (E...... conformation, stabilized by a hydrophobic hub consisting of aromatic/aromatic and aliphatic/aromatic interactions, resulting in much lower amphiphilicity. Under wide ranges of peptide loading, the microgels displayed net negative z-potential. Such negatively charged microgels do not bind to, nor lyse, bacteria...

  10. Oxidized potato starch based thermoplastic films : Effect of combination of hydrophilic and amphiphilic plasticizers

    NARCIS (Netherlands)

    Niazi, Muhammad Bilal Khan; Broekhuis, Antonius A.

    Different combinations of hydrophilic (glycerol and water) and amphiphilic (isoleucine) plasticizers were studied in the production of thermoplastic starch (TPS) powders and films from oxidized potato starch. All powder samples had an irregular and shrivelled morphology. In all mixtures containing

  11. Amphiphilic heteroarm star polymer synthesized by RAFT dispersion polymerization in water/ethanol solution.

    Science.gov (United States)

    Shi, Xiaofang; Zhou, Wei; Qiu, Qian; An, Zesheng

    2012-07-28

    Well-defined amphiphilic heteroarm core cross-linked star (CCS) polymer was efficiently synthesized by RAFT-mediated arm-first strategy in dispersion polymerization, and its direct self-assembly in water was demonstrated.

  12. Self-assembly and headgroup effect in nanostructured organogels via cationic amphiphile-graphene oxide composites.

    Directory of Open Access Journals (Sweden)

    Tifeng Jiao

    Full Text Available Self-assembly of hierarchical graphene oxide (GO-based nanomaterials with novel functions has received a great deal of attentions. In this study, nanostructured organogels based on cationic amphiphile-GO composites were prepared. The gelation behaviors of amphiphile-GO composites in organic solvents can be regulated by changing the headgroups of amphiphiles. Ammonium substituted headgroup in molecular structures in present self-assembled composites is more favorable for the gelation in comparison to pyridinium headgroup. A possible mechanism for headgroup effects on self-assembly and as-prepared nanostructures is proposed. It is believed that the present amphiphile-GO self-assembled system will provide an alternative platform for the design of new GO nanomaterials and soft matters.

  13. A molecular dynamics and circular dichroism study of a novel synthetic antimicrobial peptide

    International Nuclear Information System (INIS)

    Rodina, N P; Yudenko, A N; Terterov, I N; Eliseev, I E

    2013-01-01

    Antimicrobial peptides are a class of small, usually positively charged amphiphilic peptides that are used by the innate immune system to combat bacterial infection in multicellular eukaryotes. Antimicrobial peptides are known for their broad-spectrum antimicrobial activity and thus can be used as a basis for a development of new antibiotics against multidrug-resistant bacteria. The most challengeous task on the way to a therapeutic use of antimicrobial peptides is a rational design of new peptides with enhanced activity and reduced toxicity. Here we report a molecular dynamics and circular dichroism study of a novel synthetic antimicrobial peptide D51. This peptide was earlier designed by Loose et al. using a linguistic model of natural antimicrobial peptides. Molecular dynamics simulation of the peptide folding in explicit solvent shows fast formation of two antiparallel beta strands connected by a beta-turn that is confirmed by circular dichroism measurements. Obtained from simulation amphipatic conformation of the peptide is analysed and possible mechanism of it's interaction with bacterial membranes together with ways to enhance it's antibacterial activity are suggested

  14. Three-dimensional structure of the two-peptide bacteriocin plantaricin JK.

    Science.gov (United States)

    Rogne, Per; Haugen, Christofer; Fimland, Gunnar; Nissen-Meyer, Jon; Kristiansen, Per Eugen

    2009-09-01

    The three-dimensional structures of the two peptides, PlnJ and PlnK, that constitutes the two-peptide bacteriocin plantaricin JK have been solved in water/TFE and water/DPC-micellar solutions using nuclear magnetic resonance (NMR) spectroscopy. PlnJ, a 25 residue peptide, has an N-terminal amphiphilic alpha-helix between Trp-3 and Tyr-15. The 32 residues long PlnK forms a central amphiphilic alpha-helix between Gly-9 and Leu-24. Measurements of the effect on anti-microbial activity of single glycine replacements in PlnJ and PlnK show that Gly-13 and Gly-17 in both peptides are very sensitive, giving more than a 100-fold reduction in activity when large residues replace glycine. In variants where other glycine residues, Gly-20 in PlnJ and Gly-7, Gly-9, Gly-24 and Gly-25 in PlnK, were replaced, the activity was reduced less than 10-fold. It is proposed that the detrimental effect on activity when exchanging Gly-13 and Gly-17 in PlnJ and PlnK is a result of reduced ability of the two peptides to interact through the GxxxG-motifs constituting Gly-13 and Gly-17.

  15. Preparation of plasmonic vesicles from amphiphilic gold nanocrystals grafted with polymer brushes.

    Science.gov (United States)

    Song, Jibin; Huang, Peng; Chen, Xiaoyuan

    2016-11-01

    Gold nanovesicles contain multiple nanocrystals within a polymeric coating. The strong plasmonic coupling between adjacent nanoparticles in their vesicular shell makes ultrasensitive biosensing and bioimaging possible. In our laboratory, multifunctional plasmonic vesicles are assembled from amphiphilic gold nanocrystals (such as gold nanoparticles and gold nanorods) coated with mixed hydrophilic and hydrophobic polymer brushes or amphiphilic diblock co-polymer brushes. To fulfill the different requirements of biomedical applications, different polymers that are either pH=responsive, photoactive or biodegradable can be used to form the hydrophobic brush, while the hydrophilicity is maintained by polyethylene glycol (PEG). This protocol covers the preparation, surface functionalization and self-assembly of amphiphilic gold nanocrystals grafted covalently with polymer brushes. The protocol can be completed within 2 d. The preparation of amphiphilic gold nanocrystals, coated with amphiphilic diblock polymer brushes using a 'grafting to' method or mixed hydrophilic and hydrophobic polymer brushes using tandem 'grafting to' and 'grafting from' methods, is described. We also provide detailed procedures for the preparation and characterization of pH-responsive plasmonic gold nanovesicles from amphiphilic gold nanocrystals using a film-rehydration method that can be completed within ∼3 d.

  16. Constraining cyclic peptides to mimic protein structure motifs

    DEFF Research Database (Denmark)

    Hill, Timothy A.; Shepherd, Nicholas E.; Diness, Frederik

    2014-01-01

    Many proteins exert their biological activities through small exposed surface regions called epitopes that are folded peptides of well-defined three-dimensional structures. Short synthetic peptide sequences corresponding to these bioactive protein surfaces do not form thermodynamically stable...... and proteins, and identifies some additional restraints incorporated into natural product cyclic peptides and synthetic macrocyclic pepti-domimetics that refine peptide structure and confer biological properties....

  17. Designing anticancer peptides by constructive machine learning.

    Science.gov (United States)

    Grisoni, Francesca; Neuhaus, Claudia; Gabernet, Gisela; Müller, Alex; Hiss, Jan; Schneider, Gisbert

    2018-04-21

    Constructive machine learning enables the automated generation of novel chemical structures without the need for explicit molecular design rules. This study presents the experimental application of such a generative model to design membranolytic anticancer peptides (ACPs) de novo. A recurrent neural network with long short-term memory cells was trained on alpha-helical cationic amphipathic peptide sequences and then fine-tuned with 26 known ACPs. This optimized model was used to generate unique and novel amino acid sequences. Twelve of the peptides were synthesized and tested for their activity on MCF7 human breast adenocarcinoma cells and selectivity against human erythrocytes. Ten of these peptides were active against cancer cells. Six of the active peptides killed MCF7 cancer cells without affecting human erythrocytes with at least threefold selectivity. These results advocate constructive machine learning for the automated design of peptides with desired biological activities. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Antimicrobial Peptides

    Directory of Open Access Journals (Sweden)

    Ali Adem Bahar

    2013-11-01

    Full Text Available The rapid increase in drug-resistant infections has presented a serious challenge to antimicrobial therapies. The failure of the most potent antibiotics to kill “superbugs” emphasizes the urgent need to develop other control agents. Here we review the history and new development of antimicrobial peptides (AMPs, a growing class of natural and synthetic peptides with a wide spectrum of targets including viruses, bacteria, fungi, and parasites. We summarize the major types of AMPs, their modes of action, and the common mechanisms of AMP resistance. In addition, we discuss the principles for designing effective AMPs and the potential of using AMPs to control biofilms (multicellular structures of bacteria embedded in extracellular matrixes and persister cells (dormant phenotypic variants of bacterial cells that are highly tolerant to antibiotics.

  19. Lipid shape is a key factor for membrane interactions of amphipathic helical peptides.

    Science.gov (United States)

    Strandberg, Erik; Tiltak, Deniz; Ehni, Sebastian; Wadhwani, Parvesh; Ulrich, Anne S

    2012-07-01

    The membrane alignment of the amphiphilic alpha-helical model peptide MSI-103 (sequence [KIAGKIA]3-NH2) was examined by solid state 2H-NMR in different lipid systems by systematically varying the acyl chain length and degree of saturation, the lipid head group type, and the peptide-to-lipid molar ratio. In liquid crystalline phosphatidylcholine (PC) lipids with saturated chains, the amphiphilic helix changes its orientation from a surface-bound "S-state" to a tilted "T-state" with increasing peptide concentration. In PC lipids with unsaturated chains, on the other hand, the S-state is found throughout all concentrations. Using phosphatidylethanolamine lipids with a small head group or by addition of lyso-lipids with only one acyl chain, the spontaneous curvature of the bilayer was purposefully changed. In the first case with a negative curvature only the S-state was found, whereas in systems with a positive curvature the peptide preferred the obliquely immersed T-state at high concentration. The orientation of MSI-103 thus correlates very well with the shape of the lipid molecules constituting the membrane. Lipid charge, on the other hand, was found to affect only the initial electrostatic attraction to the membrane surface but not the alignment preferences. In bilayers that are "sealed" with 20% cholesterol, MSI-103 cannot bind in a well-oriented manner and forms immobilized aggregates instead. We conclude that the curvature properties of a membrane are a key factor in the interactions of amphiphilic helical peptides in general, whose re-alignment and immersion preferences may thus be inferred in a straightforward manner from the lipid-shape concept.

  20. Biodegradable Peptide-Silica Nanodonuts.

    Science.gov (United States)

    Maggini, Laura; Travaglini, Leana; Cabrera, Ingrid; Castro-Hartmann, Pablo; De Cola, Luisa

    2016-03-07

    We report hybrid organosilica toroidal particles containing a short peptide sequence as the organic component of the hybrid systems. Once internalised in cancer cells, the presence of the peptide allows for interaction with peptidase enzymes, which attack the nanocarrier effectively triggering its structural breakdown. Moreover, these biodegradable nanovectors are characterised by high cellular uptake and exocytosis, showing great potential as biodegradable drug carriers. To demonstrate this feature, doxorubicin was employed and its delivery in HeLa cells investigated. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Toward Personalized Peptide-Based Cancer Nanovaccines: A Facile and Versatile Synthetic Approach.

    Science.gov (United States)

    Kakwere, Hamilton; Ingham, Elizabeth S; Allen, Riley; Mahakian, Lisa M; Tam, Sarah M; Zhang, Hua; Silvestrini, Matthew T; Lewis, Jamal S; Ferrara, Katherine W

    2017-11-15

    Personalized cancer vaccines (PCVs) are receiving attention as an avenue for cancer immunotherapy. PCVs employ immunogenic peptide epitopes capable of stimulating the immune system to destroy cancer cells with great specificity. Challenges associated with effective delivery of these peptides include poor solubility of hydrophobic sequences, rapid clearance, and poor immunogenicity, among others. The incorporation of peptides into nanoparticles has the potential to overcome these challenges, but the broad range of functionalities found in amino acids presents a challenge to conjugation due to possible interferences and lack of reaction specificity. Herein, a facile and versatile approach to generating nanosized PCVs under mild nonstringent conditions is reported. Following a simple two-step semibatch synthetic approach, amphiphilic hyperbranched polymer-peptide conjugates were prepared by the conjugation of melanoma antigen peptides, either TRP2 (hydrophobic) or MUT30 (hydrophilic), to an alkyne functionalized core via strain-promoted azide-alkyne click chemistry. Self-assembly of the amphiphiles gave spherical nanovaccines (by transmission electron microscopy) with sizes in the range of 10-30 nm (by dynamic light scattering). Fluorescently labeled nanovaccines were prepared to investigate the cellular uptake by antigen presenting cells (dendritic cells), and uptake was confirmed by flow cytometry and microscopy. The TRP2 nanovaccine was taken up the most followed by MUT30 nanoparticles and, finally, nanoparticles without peptide. The nanovaccines showed good biocompatibility against B16-F10 cells, yet the TRP2 peptide showed signs of toxicity, possibly due to its hydrophobicity. A test for immunogenicity revealed that the nanovaccines were poorly immunogenic, implying the need for an adjuvant when administered in vivo. Treatment of mice with melanoma tumors showed that in combination with adjuvant, CpG, groups with the peptide nanovaccines slowed tumor growth and

  2. Modification of nanofibrillated cellulose using amphiphilic block-structured galactoglucomannans.

    Science.gov (United States)

    Lozhechnikova, Alina; Dax, Daniel; Vartiainen, Jari; Willför, Stefan; Xu, Chunlin; Österberg, Monika

    2014-09-22

    Nanofibrillated cellulose (NFC) and hemicelluloses have shown to be highly promising renewable components both as barrier materials and in novel biocomposites. However, the hydrophilic nature of these materials restricts their use in some applications. In this work, the usability of modified O-acetyl galactoglucomannan (GGM) for modification of NFC surface properties was studied. Four GGM-block-structured, amphiphilic derivatives were synthesized using either fatty acids or polydimethylsiloxane as hydrophobic tails. The adsorption of these GGM derivatives was consecutively examined in aqueous solution using a quartz crystal microbalance with dissipation monitoring (QCM-D). It was found that the hydrophobic tails did not hinder adsorption of the GGM derivatives to cellulose, which was concluded to be due to the presence of the native GGM-block with high affinity to cellulose. The layer properties of the adsorbed block-co-polymers were discussed and evaluated. Self-standing NFC films were further prepared and coated with the GGM derivatives and the effect of the surface modification on wetting properties and oxygen permeability (OP) of the modified films was assessed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Redox-switched amphiphilic ionic liquid behavior in aqueous solution.

    Science.gov (United States)

    Chamiot, Bénédicte; Rizzi, Cécile; Gaillon, Laurent; Sirieix-Plénet, Juliette; Lelièvre, Joël

    2009-02-03

    A new redox amphiphilic ionic liquid (AIL) containing ferrocene as a redox-active group was synthesized, 1-(11-ferrocenylundecyl)-3-methylimidazolium bromide (Fc11MIm+). Adsorption and aggregation of both reduced and oxidized forms of this ferrocenated AIL in aqueous solution were studied by surface tension measurements. The micellization was favored for the reduced ferrocenated AIL (Fc11MIm+) as compared with the oxidized ferrocenated AIL (Fc+11MIm+). Minimum areas at the air/aqueous solution interface were identical whereas limiting surface tensions were slightly different. This corroborated the formation of an expanded monolayer of redox active AIL at the interface. The electrochemical behavior of redox active AIL was investigated. The electrochemical responses of Fc11MIm+ aqueous solution interestingly differed, depending on its concentration. Below the cmc, the electrochemical reaction was dominated by ferrocenated AIL adsorbed onto the electrode surface; then above the cmc, it was controlled by the Fc11MIm+ diffusing to the electrode. For the latter, the electrochemical mechanism was suggested to couple with the disruption reaction of the reduced form micelles.

  4. The role of polar and facial amphipathic character in determining lipopolysaccharide-binding properties in synthetic cationic peptides.

    Science.gov (United States)

    David, S A; Awasthi, S K; Balaram, P

    2000-01-01

    Two series of peptides, designated K and NK were synthesized and tested for lipid A binding and neutralizing properties. K2, which has an 11-residue amphiphilic core, and a branched N-terminus bearing two branched lysinyl residues does not bind lipid A, while NK2, also with an 11-residue amphiphilic core comprised entirely of non-ionizable residues, and a similarly branched, cationic N-terminus, binds lipid A very weakly. Both peptides do not inhibit lipopolysaccharide (LPS) activity in the Limulus assay, nor do they inhibit LPS-induced TNF-alpha and NO production in J774 cells. These results are entirely unlike a homologous peptide with an exclusively hydrophobic core whose LPS-binding and neutralizing properties are very similar to that of polymyxin B [David SA, Awasthi SK, Wiese A et al. Characterization of the interactions of a polycationic, amphiphilic, terminally branched oligopeptide with lipid A and lipopolysaccharide from the deep rough mutant of Salmonella minnesota. J Endotoxin Res 1996; 3: 369-379]. These data suggest that a clear segregation of charged and apolar domains is crucial in molecules designed for purposes of LPS sequestration and that head-tail (polar) orientation of the cationic/hydrophobic regions is preferable to molecules with mixed or facial cationic/amphipathic character.

  5. Synthetic antifreeze peptide

    OpenAIRE

    1991-01-01

    A synthetic antifreeze peptide and a synthetic gene coding for the antifreeze peptide have been produced. The antifreeze peptide has a greater number of repeating amino acid sequences than is present in the native antifreeze peptides from winter flounder upon which the synthetic antifreeze peptide was modeled. Each repeating amino acid sequence has two polar amino acid residues which are spaced a controlled distance apart so that the antifreeze peptide may inhibit ice formation. The synthetic...

  6. Controllable Self-Assembly of Amphiphilic Zwitterionic PBI Towards Tunable Surface Wettability of the Nanostructures.

    Science.gov (United States)

    Ye, Yong; Lü, Baozhong; Cheng, Wenyu; Wu, Zhen; Wei, Jie; Yin, Meizhen

    2017-05-04

    Amphiphilic molecules have received wide attention as they possess both hydrophobic and hydrophilic properties, and can form diverse nanostructures in selective solvents. Herein, we report an asymmetric amphiphilic zwitterionic perylene bisimide (AZP) with an octyl chain and a zwitterionic group on the opposite imide positions of perylene tetracarboxylic dianhydride. The controllable nanostructures of AZP with tunable hydrophilic/hydrophobic surface have been investigated through solvent-dependent amphiphilic self-assembly as confirmed by SEM, TEM, and contact angle measurements. The planar perylene core of AZP contributes to strong π-π stacking, while the amphiphilic balance of asymmetric AZP adjusts the self-assembly property. Additionally, due to intermolecular π-π stacking and solvent-solute interactions, AZP could self-assemble into hydrophilic microtubes in a polar solvent (acetone) and hydrophobic nanofibers in an apolar solvent (hexane). This facile method provides a new pathway for controlling the surface properties based on an asymmetric amphiphilic zwitterionic perylene bisimide. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Effect of sequence on the ionization behavior of a series of amphiphilic polypeptides.

    Science.gov (United States)

    Fowler, Michael; Siddique, Bushra; Duhamel, Jean

    2013-04-09

    The behavior of five polypeptides made of hydrophilic and pH-responsive aspartic acid (Asp) and hydrophobic phenylalanine (Phe), which had been prepared by stitching together short well-defined sequences of Asp and Phe, was studied as a function of pH. The effect of pH on these polypeptides referred to as (Asp3Phe1)n, (Asp2Phe1)n, (Asp1Phe1)n, (Asp1Phe2)n, and (Asp1Phe3)n varied dramatically depending on their constituting sequence. The more hydrophobic polypeptides (Asp1Phe2)n and (Asp1Phe3)n behaved as if the Asp's were isolated from each other and showed an apparent pKa (pKa(app)) that remained constant with level of ionization (α = [Asp(-)]/[Asp]total) and equaled 5.4 and 6.4, respectively. The more hydrophilic polypeptides (Asp3Phe1)n and (Asp2Phe1)n behaved like weak polyacids showing a linear increase in pKa(app) with increasing α. The pKa(app) of (Asp1Phe1)n showed a trend as a function of α intermediate between the Asp-rich and Phe-rich polypeptides, behaving as if the Asp's were isolated at low α values (0.35). The effect that α, and thus the charge density of the polypeptides, had on the collapse and aggregation of the polypeptides was characterized by conducting static light scattering and fluorescence measurements. Static light scattering measurements demonstrated that all polypeptides precipitated and aggregated in solution at a critical charge density of 0.2. Fluorescence measurements with pyrene indicated that this behavior was due to the formation of Phe aggregates in water. Together, these experiments provide a complete description of how pH affects the behavior of a series of unique amphiphilic polypeptides designed with a well-defined sequence.

  8. Multifunctional hybrid networks based on self assembling peptide sequences

    Science.gov (United States)

    Sathaye, Sameer

    The overall aim of this dissertation is to achieve a comprehensive correlation between the molecular level changes in primary amino acid sequences of amphiphilic beta-hairpin peptides and their consequent solution-assembly properties and bulk network hydrogel behavior. This has been accomplished using two broad approaches. In the first approach, amino acid substitutions were made to peptide sequence MAX1 such that the hydrophobic surfaces of the folded beta-hairpins from the peptides demonstrate shape specificity in hydrophobic interactions with other beta-hairpins during the assembly process, thereby causing changes to the peptide nanostructure and bulk rheological properties of hydrogels formed from the peptides. Steric lock and key complementary hydrophobic interactions were designed to occur between two beta-hairpin molecules of a single molecule, LNK1 during beta-sheet fibrillar assembly of LNK1. Experimental results from circular dichroism, transmission electron microscopy and oscillatory rheology collectively indicate that the molecular design of the LNK1 peptide can be assigned the cause of the drastically different behavior of the networks relative to MAX1. The results indicate elimination or significant reduction of fibrillar branching due to steric complementarity in LNK1 that does not exist in MAX1, thus supporting the original hypothesis. As an extension of the designed steric lock and key complementarity between two beta-hairpin molecules of the same peptide molecule. LNK1, three new pairs of peptide molecules LP1-KP1, LP2-KP2 and LP3-KP3 that resemble complementary 'wedge' and 'trough' shapes when folded into beta-hairpins were designed and studied. All six peptides individually and when blended with their corresponding shape complement formed fibrillar nanostructures with non-uniform thickness values. Loose packing in the assembled structures was observed in all the new peptides as compared to the uniform tight packing in MAX1 by SANS analysis. This

  9. Molecular Engineering Solutions for Therapeutic Peptide Delivery.

    Energy Technology Data Exchange (ETDEWEB)

    Acar, Handan; Ting, Jeffrey M.; Srivastava, Samanvaya; LaBelle, James L.; Tirrell, Matthew V.

    2017-11-07

    Proteins and their interactions in and out of cells must be well-orchestrated for the healthy functioning and regulation of the body. Even the slightest disharmony can cause diseases. Therapeutic peptides are short amino acid sequences (generally considered <50 amino acids) that can naturally mimic the binding interfaces between proteins and thus, influence protein-protein interactions. Because of their fidelity of binding, peptides are a promising next generation of personalized medicines to reinstate biological harmony. Peptides as a group are highly selective, relatively safe, and biocompatible. However, they are also vulnerable to many in vivo pharmacologic barriers limiting their clinical translation. Current advances in molecular, chemical, and nanoparticle engineering are helping to overcome these previously insurmountable obstacles and improve the future of peptides as active and highly selective therapeutics. In this review, we focus on self-assembled vehicles as nanoparticles to carry and protect therapeutic peptides through this journey, and deliver them to the desired tissue.

  10. Beta-Sheet-Forming, Self-Assembled Peptide Nanomaterials towards Optical, Energy, and Healthcare Applications.

    Science.gov (United States)

    Kim, Sungjin; Kim, Jae Hong; Lee, Joon Seok; Park, Chan Beum

    2015-08-12

    Peptide self-assembly is an attractive route for the synthesis of intricate organic nanostructures that possess remarkable structural variety and biocompatibility. Recent studies on peptide-based, self-assembled materials have expanded beyond the construction of high-order architectures; they are now reporting new functional materials that have application in the emerging fields such as artificial photosynthesis and rechargeable batteries. Nevertheless, there have been few reviews particularly concentrating on such versatile, emerging applications. Herein, recent advances in the synthesis of self-assembled peptide nanomaterials (e.g., cross β-sheet-based amyloid nanostructures, peptide amphiphiles) are selectively reviewed and their new applications in diverse, interdisciplinary fields are described, ranging from optics and energy storage/conversion to healthcare. The applications of peptide-based self-assembled materials in unconventional fields are also highlighted, such as photoluminescent peptide nanostructures, artificial photosynthetic peptide nanomaterials, and lithium-ion battery components. The relation of such functional materials to the rapidly progressing biomedical applications of peptide self-assembly, which include biosensors/chips and regenerative medicine, are discussed. The combination of strategies shown in these applications would further promote the discovery of novel, functional, small materials. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Adaptive chemistry of bifunctional gold nanoparticles at the air/water interface. A synchrotron X-ray study of giant amphiphiles

    DEFF Research Database (Denmark)

    Nørgaard, K.; Weygand, M.J.; Kjær, K.

    2004-01-01

    A series of ligand stabilized gold nanoparticles with diameters close to 3 nm were studied as Langmuir monolayers at the air/water interface by synchrotron X-ray diffraction and reflectivity. Alkylthiols with different length and/or terminal functional group (hydrophilic or hydrophobic) were...... of environmental responsiveness, as they adapt to an amphiphilic distribution of ligands around the gold core when spread at the water surface. Likewise nanoparticles of mixed long and short alkyl chains respond to lateral pressure by adopting a structure where the short alkyl chains determine the in-plane nearest...... of the monolayers to a solid support using the Langmuir-Schaefer technique. The combination of the different techniques produce a very consistent picture of the structure and adaptive chemical nature of the nanoparticles studied, and reveal a surprisingly monodisperse particle distribution centered around 140 atoms...

  12. Colloidosomes formed by nonpolar/polar/nonpolar nanoball amphiphiles

    International Nuclear Information System (INIS)

    Chang, Hung-Yu; Sheng, Yu-Jane; Tu, Sheng-Hung; Tsao, Heng-Kwong

    2014-01-01

    Fullerene-based amphiphiles are able to form bilayer vesicles in aqueous solution. In this study, the self-assembly behavior of polymer-tethered nanoballs (NBs) with nonpolar/polar/nonpolar (n-p-n ′ ) motif in a selective solvent is investigated by dissipative particle dynamics. A model NB bears two hydrophobic polymeric arms (n ′ -part) tethered on an extremely hydrophobic NB (n-part) with hydrophilic patch (p-part) patterned on its surface. Dependent on the hydrophobicity and length of tethered arms, three types of aggregates are exhibited, including NB vesicle, core-shell micelle, and segmented-worm. NB vesicles are developed for a wide range of hydrophobic arm lengths. The presence of tethered arms perturbs the bilayer structure formed by NBs. The structural properties including the order parameter, membrane thickness, and area density of the inner leaflet decrease with increasing the arm length. These results indicate that for NBs with longer arms, the extent of interdigitation in the membrane rises so that the overcrowded arms in the inner corona are relaxed. The transport and mechanical properties are evaluated as well. As the arm length grows, the permeability increases significantly because the steric bulk of tethered arms loosens the packing of NBs. By contrast, the membrane tension decreases owing to the reduction of NB/solvent contacts by the polymer corona. Although fusion can reduce membrane tension, NB vesicles show strong resistance to fusion. Moreover, the size-dependent behavior observed in small liposomes is not significant for NB vesicles due to isotropic geometry of NB. Our simulation results are consistent with the experimental findings

  13. Colloidosomes formed by nonpolar/polar/nonpolar nanoball amphiphiles

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Hung-Yu; Sheng, Yu-Jane, E-mail: yjsheng@ntu.edu.tw, E-mail: hktsao@cc.ncu.edu.tw [Department of Chemical Engineering, National Taiwan University, Taipei 106, Taiwan (China); Tu, Sheng-Hung [Department of Chemical and Materials Engineering, National Central University, Jhongli 320, Taiwan (China); Tsao, Heng-Kwong, E-mail: yjsheng@ntu.edu.tw, E-mail: hktsao@cc.ncu.edu.tw [Department of Chemical and Materials Engineering and Department of Physics, National Central University, Jhongli 320, Taiwan (China)

    2014-08-07

    Fullerene-based amphiphiles are able to form bilayer vesicles in aqueous solution. In this study, the self-assembly behavior of polymer-tethered nanoballs (NBs) with nonpolar/polar/nonpolar (n-p-n{sup ′}) motif in a selective solvent is investigated by dissipative particle dynamics. A model NB bears two hydrophobic polymeric arms (n{sup ′}-part) tethered on an extremely hydrophobic NB (n-part) with hydrophilic patch (p-part) patterned on its surface. Dependent on the hydrophobicity and length of tethered arms, three types of aggregates are exhibited, including NB vesicle, core-shell micelle, and segmented-worm. NB vesicles are developed for a wide range of hydrophobic arm lengths. The presence of tethered arms perturbs the bilayer structure formed by NBs. The structural properties including the order parameter, membrane thickness, and area density of the inner leaflet decrease with increasing the arm length. These results indicate that for NBs with longer arms, the extent of interdigitation in the membrane rises so that the overcrowded arms in the inner corona are relaxed. The transport and mechanical properties are evaluated as well. As the arm length grows, the permeability increases significantly because the steric bulk of tethered arms loosens the packing of NBs. By contrast, the membrane tension decreases owing to the reduction of NB/solvent contacts by the polymer corona. Although fusion can reduce membrane tension, NB vesicles show strong resistance to fusion. Moreover, the size-dependent behavior observed in small liposomes is not significant for NB vesicles due to isotropic geometry of NB. Our simulation results are consistent with the experimental findings.

  14. Soft/Hard-Coupled Amphiphilic Polymer Nanospheres for Water Lubrication.

    Science.gov (United States)

    Li, Zhaoxia; Ma, Shuanhong; Zhang, Ga; Wang, Daoai; Zhou, Feng

    2018-03-14

    Amphiphilic polymer nanospheres of poly(3-sulfopropyl methacrylate potassium salt- co-styrene) [P(SPMA- co-St)] were prepared by a simple soap-free emulsion polymerization method and used as efficient water lubrication additives to enhance the antiwear behaviors of the Ti 6 Al 4 V alloy. The monodisperse and flexible P(SPMA- co-St) bicomponent copolymer nanospheres were synthesized with a controllable manner by adjusting the mass fraction ratio of the monomers, with the hydrophobic polystyrene (PSt) as the hard skeletal carrier component and the hydrophilic PSPMA with a hydration layer structure as the soft lubrication layer in the course of friction. The influences of the monomer concentration, the copolymer nanosphere additive content, the load, and the frequency of the friction conditions on their tribological properties were studied in detail, and a probable antiwear mechanism of the soft/hard-coupled copolymer nanospheres under water lubrication was also proposed. The results show that compared with pure PSt, the P(SPMA- co-St) polymer nanospheres exhibited better antiwear property as an additive for water lubrication, and the friction coefficient and the wear volume first decreased and then increased with the increase of the SPMA content, indicating that the hydrophilic SPMA has a significant effect on lubrication properties owing to its hydration performance. Furthermore, with the increase of polymer nanosphere concentration, the friction coefficient and wear amount also decreased to a stable and low value at a saturation concentration of 1 wt %. The flexible polymer nanospheres with a hydrophilic soft SPMA shell and a rigid PSt core exhibited good friction-reduction and antiwear performance as lubrication additives, indicating their promising and potential applications in water lubrication and biological lubrication.

  15. Amphiphilic block co-polymers: preparation and application in nanodrug and gene delivery.

    Science.gov (United States)

    Xiong, Xiao-Bing; Binkhathlan, Ziyad; Molavi, Ommoleila; Lavasanifar, Afsaneh

    2012-07-01

    Self-assembly of amphiphilic block co-polymers composed of poly(ethylene oxide) (PEO) as the hydrophilic block and poly(ether)s, poly(amino acid)s, poly(ester)s and polypropyleneoxide (PPO) as the hydrophobic block can lead to the formation of nanoscopic structures of different morphologies. These structures have been the subject of extensive research in the past decade as artificial mimics of lipoproteins and viral vectors for drug and gene delivery. The aim of this review is to provide an overview of the synthesis of commonly used amphiphilic block co-polymers. It will also briefly go over some pharmaceutical applications of amphiphilic block co-polymers as "nanodelivery systems" for small molecules and gene therapeutics. Copyright © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  16. Where surface physics and fluid dynamics meet: rupture of an amphiphile layer by fluid flow.

    Science.gov (United States)

    Bandi, M M; Goldburg, W I; Cressman, J R; Kellay, H

    2006-03-14

    We investigate the fluctuating pattern created by a jet of fluid impingent upon an amphiphile-covered surface. This microscopically thin layer is initially covered with 50 microm floating particles so that the layer can be visualized. A vertical jet of water located below the surface and directed upward drives a hole in this layer. The hole is particle-free and is surrounded by the particle-laden amphiphile region. The jet ruptures the amphiphile layer creating a particle-free region that is surrounded by the particle-covered surface. The aim of the experiment is to understand the (fluctuating) shape of the ramified interface between the particle-laden and particle-free regions.

  17. Magnetic amphiphilic hybrid carbon nanotubes containing N-doped and undoped sections: powerful tensioactive nanostructures

    Science.gov (United States)

    Purceno, Aluir D.; Machado, Bruno F.; Teixeira, Ana Paula C.; Medeiros, Tayline V.; Benyounes, Anas; Beausoleil, Julien; Menezes, Helvecio C.; Cardeal, Zenilda L.; Lago, Rochel M.; Serp, Philippe

    2014-11-01

    In this work, unique amphiphilic magnetic hybrid carbon nanotubes (CNTs) are synthesized and used as tensioactive nanostructures in different applications. These CNTs interact very well with aqueous media due to the hydrophilic N-doped section, whereas the undoped hydrophobic one has strong affinity for organic molecules. The amphiphilic character combined with the magnetic properties of these CNTs opens the door to completely new and exciting applications in adsorption science and catalysis. These amphiphilic N-doped CNTs can also be used as powerful tensioactive emulsification structures. They can emulsify water/organic mixtures and by a simple magnetic separation the emulsion can be easily broken. We demonstrate the application of these CNTs in the efficient adsorption of various molecules, in addition to promoting biphasic processes in three different reactions, i.e. transesterification of soybean oil, quinoline extractive oxidation with H2O2 and a metal-catalyzed aqueous oxidation of heptanol with molecular oxygen.In this work, unique amphiphilic magnetic hybrid carbon nanotubes (CNTs) are synthesized and used as tensioactive nanostructures in different applications. These CNTs interact very well with aqueous media due to the hydrophilic N-doped section, whereas the undoped hydrophobic one has strong affinity for organic molecules. The amphiphilic character combined with the magnetic properties of these CNTs opens the door to completely new and exciting applications in adsorption science and catalysis. These amphiphilic N-doped CNTs can also be used as powerful tensioactive emulsification structures. They can emulsify water/organic mixtures and by a simple magnetic separation the emulsion can be easily broken. We demonstrate the application of these CNTs in the efficient adsorption of various molecules, in addition to promoting biphasic processes in three different reactions, i.e. transesterification of soybean oil, quinoline extractive oxidation with H2O2 and

  18. Potential of acylated peptides to target the influenza A virus

    Directory of Open Access Journals (Sweden)

    Daniel Lauster

    2015-04-01

    Full Text Available For antiviral drug design, especially in the field of influenza virus research, potent multivalent inhibitors raise high expectations for combating epidemics and pandemics. Among a large variety of covalent and non-covalent scaffold systems for a multivalent display of inhibitors, we created a simple supramolecular platform to enhance the antiviral effect of our recently developed antiviral Peptide B (PeBGF, preventing binding of influenza virus to the host cell. By conjugating the peptide with stearic acid to create a higher-order structure with a multivalent display, we could significantly enhance the inhibitory effect against the serotypes of both human pathogenic influenza virus A/Aichi/2/1968 H3N2, and avian pathogenic A/FPV/Rostock/34 H7N1 in the hemagglutination inhibition assay. Further, the inhibitory potential of stearylated PeBGF (C18-PeBGF was investigated by infection inhibition assays, in which we achieved low micromolar inhibition constants against both viral strains. In addition, we compared C18-PeBGF to other published amphiphilic peptide inhibitors, such as the stearylated sugar receptor mimicking peptide (Matsubara et al. 2010, and the “Entry Blocker” (EB (Jones et al. 2006, with respect to their antiviral activity against infection by Influenza A Virus (IAV H3N2. However, while this strategy seems at a first glance promising, the native situation is quite different from our experimental model settings. First, we found a strong potential of those peptides to form large amyloid-like supramolecular assemblies. Second, in vivo, the large excess of cell surface membranes provides an unspecific target for the stearylated peptides. We show that acylated peptides insert into the lipid phase of such membranes. Eventually, our study reveals serious limitations of this type of self-assembling IAV inhibitors.

  19. Catalytic Y-tailed amphiphilic homopolymers - aqueous nanoreactors for high activity, low loading SCS pincer catalysts.

    Science.gov (United States)

    Patterson, Joseph P; Cotanda, Pepa; Kelley, Elizabeth G; Moughton, Adam O; Lu, Annhelen; Epps, Thomas H; O'Reilly, Rachel K

    2013-01-01

    A new amphiphilic homopolymer bearing an SCS pincer palladium complex has been synthesized by reversible addition fragmentation chain transfer polymerization. The amphiphile has been shown to form spherical and worm-like micelles in water by cryogenic transmission electron microscopy and small angle neutron scattering. Segregation of reactive components within the palladium containing core results in increased catalytic activity of the pincer compound compared to small molecule analogues. This allows carbon-carbon bond forming reactions to be performed in water with reduced catalyst loadings and enhanced activity.

  20. Isolation of biologically active peptides from the venom of Japanese carpenter bee, Xylocopa appendiculata.

    Science.gov (United States)

    Kawakami, Hiroko; Goto, Shin G; Murata, Kazuya; Matsuda, Hideaki; Shigeri, Yasushi; Imura, Tomohiro; Inagaki, Hidetoshi; Shinada, Tetsuro

    2017-01-01

    Mass spectrometry-guided venom peptide profiling is a powerful tool to explore novel substances from venomous animals in a highly sensitive manner. In this study, this peptide profiling approach is successfully applied to explore the venom peptides of a Japanese solitary carpenter bee, Xylocopa appendiculata (Hymenoptera: Apoidea: Apidae: Anthophila: Xylocopinae: Xylocopini). Although interesting biological effects of the crude venom of carpenter bees have been reported, the structure and biological function of the venom peptides have not been elucidated yet. The venom peptide profiling of the crude venom of X. appendiculata was performed by matrix-assisted laser desorption/ionization-time of flight mass spectroscopy. The venom was purified by a reverse-phase HPLC. The purified peptides were subjected to the Edman degradation, MS/MS analysis, and/or molecular cloning methods for peptide sequencing. Biological and functional characterization was performed by circular dichroism analysis, liposome leakage assay, and antimicrobial, histamine releasing and hemolytic activity tests. Three novel peptides with m / z 16508, 1939.3, and 1900.3 were isolated from the venom of X. appendiculata . The peptide with m / z 16508 was characterized as a secretory phospholipase A 2 (PLA 2 ) homolog in which the characteristic cysteine residues as well as the active site residues found in bee PLA 2 s are highly conserved. Two novel peptides with m/z 1939.3 and m/z 1900.3 were named as Xac-1 and Xac-2, respectively. These peptides are found to be amphiphilic and displayed antimicrobial and hemolytic activities. The potency was almost the same as that of mastoparan isolated from the wasp venom. We found three novel biologically active peptides in the venom of X. appendiculata and analyzed their molecular functions, and compared their sequential homology to discuss their molecular diversity. Highly sensitive mass analysis plays an important role in this study.

  1. Human peptide transporters

    DEFF Research Database (Denmark)

    Nielsen, Carsten Uhd; Brodin, Birger; Jørgensen, Flemming Steen

    2002-01-01

    Peptide transporters are epithelial solute carriers. Their functional role has been characterised in the small intestine and proximal tubules, where they are involved in absorption of dietary peptides and peptide reabsorption, respectively. Currently, two peptide transporters, PepT1 and PepT2, wh...

  2. [SYNTHETIC PEPTIDE VACCINES].

    Science.gov (United States)

    Sergeyev, O V; Barinsky, I F

    2016-01-01

    An update on the development and trials of synthetic peptide vaccines is reviewed. The review considers the successful examples of specific protection as a result of immunization with synthetic peptides using various protocols. The importance of conformation for the immunogenicity of the peptide is pointed out. An alternative strategy of the protection of the organism against the infection using synthetic peptides is suggested.

  3. The effect of amphiphilic polymers with a continuous amphiphilicity profile on the membrane properties in a bicontinuous microemulsions studied by neutron scattering

    Science.gov (United States)

    Klemmer, Helge F. M.; Frielinghaus, Henrich; Allgaier, Jürgen; Ohl, Michael; Holderer, Olaf

    2017-06-01

    Microemulsion systems consisting of oil, water and surfactant have been studied with neutron scattering techniques. The amount of surfactant needed to form a microemulsion can be dramatically reduced by the addition of small amounts of amphiphilic block copolymers (boosting effect). Here, we studied the influence of block copolymers with gradually changing amphiphilicity from hydrophilic to hydrophobic. Small angle neutron scattering (SANS), neutron spin echo spectroscopy (NSE) and phase diagram measurements in combination give access to the elastic properties of the membrane. The underlying NSE experiments for this interpretation rely on smallest changes of the relaxation curves (of ca. 1% steps) for still small changes of the bending rigidity (of ca. 10% steps). This high reliability of the experiments conducted at the SNS-NSE displays the accuracy of the instrument itself and the latest developments of the evaluation software, which were necessary to interpret such tiny changes of the bending rigidity reliably.

  4. Modern treatment of short bowel syndrome

    DEFF Research Database (Denmark)

    Jeppesen, Palle B

    2013-01-01

    Recently, the US Food and Drug Administration and the European Medicines Agency approved the glucagon-like peptide 2 analogue, teduglutide, for the treatment of short bowel syndrome (SBS), and this review describes the physiological basis for its clinical use.......Recently, the US Food and Drug Administration and the European Medicines Agency approved the glucagon-like peptide 2 analogue, teduglutide, for the treatment of short bowel syndrome (SBS), and this review describes the physiological basis for its clinical use....

  5. Charge-Transfer Supra-Amphiphiles Built by Water-Soluble Tetrathiafulvalenes and Viologen-Containing Amphiphiles: Supramolecular Nanoassemblies with Modifiable Dimensions.

    Science.gov (United States)

    Lv, Zhong-Peng; Chen, Bin; Wang, Hai-Ying; Wu, Yue; Zuo, Jing-Lin

    2015-08-05

    In this study, multidimensional nanoassemblies with various morphologies such as nanosheets, nanorods, and nanofibers are developed via charge-transfer interaction and supra-amphiphile self-assembling in aqueous phase. The charge-transfer interactions between tetrathiafulvalene derivatives (TTFs) and methyl viologen derivatives (MVs) have been confirmed by the characteristic charger-transfer absorption. (1) H NMR and electrospray ionizsation mass spectrometry (ESI-MS) analyses also indicate supra-amphiphiles are formed by the combination of TTFs and MVs head group through charge-transfer interaction and Coulombic force. X-ray single crystal structural studies, transmission electron microscopy (TEM), and scanning electron microscopy (SEM) reveal that both linkage pattern of TTFs in hydrophilic part and alkane chain structure in hydrophobic part have significant influence on nanoassemblies morphology and microstructure. Moreover, gold nanoparticles (AuNPs) are introduced in the above supramolecular nanoassemblies to construct a supra-amphiphile-driven organic-AuNPs assembly system. AuNPs could be assembled into 1D-3D structures by adding different amount of MVs. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Sum Frequency Generation Vibrational Spectroscopy Studies on ModelPeptide Adsorption at the Hydrophobic Solid-Water and HydrophilicSolid-Water Interfaces

    Energy Technology Data Exchange (ETDEWEB)

    York, Roger L. [Univ. of California, Berkeley, CA (United States)

    2007-01-01

    Sum frequency generation (SFG) vibrational spectroscopy has been used to study the interfacial structure of several polypeptides and amino acids adsorbed to hydrophobic and hydrophilic surfaces under a variety of experimental conditions. Peptide sequence, peptide chain length, peptide hydrophobicity, peptide side-chain type, surface hydrophobicity, and solution ionic strength all affect an adsorbed peptide's interfacial structure. Herein, it is demonstrated that with the choice of simple, model peptides and amino acids, surface specific SFG vibrational spectroscopy can be a powerful tool to elucidate the interfacial structure of these adsorbates. Herein, four experiments are described. In one, a series of isosequential amphiphilic peptides are synthesized and studied when adsorbed to both hydrophobic and hydrophilic surfaces. On hydrophobic surfaces of deuterated polystyrene, it was determined that the hydrophobic part of the peptide is ordered at the solid-liquid interface, while the hydrophilic part of the peptide appears to have a random orientation at this interface. On a hydrophilic surface of silica, it was determined that an ordered peptide was only observed if a peptide had stable secondary structure in solution. In another experiment, the interfacial structure of a model amphiphilic peptide was studied as a function of the ionic strength of the solution, a parameter that could change the peptide's secondary structure in solution. It was determined that on a hydrophobic surface, the peptide's interfacial structure was independent of its structure in solution. This was in contrast to the adsorbed structure on a hydrophilic surface, where the peptide's interfacial structure showed a strong dependence on its solution secondary structure. In a third experiment, the SFG spectra of lysine and proline amino acids on both hydrophobic and hydrophilic surfaces were obtained by using a different experimental geometry that increases the SFG signal

  7. A synthetic strategy for novel nonsymmetrical bola amphiphiles based on carbohydrates

    NARCIS (Netherlands)

    Schuur, B; Wagenaar, Anno; Heeres, Andre; Heeres, Erik H. J.

    2004-01-01

    A number of novel nonionic bolaform amphiphiles with nonidentical aldityl head groups, 1-(1-deoxy-D-galactitol-l-ylamino)-6-(1-deoxy-D- galactitol-1-ylamino)hexane (4a), 1-(1-deoxy-D-mannitol-1-ylamino)-6-(1-deoxy-D-glucitol-1-ylamino)hexane (4b). and

  8. Functionalized surfaces of polylactide modified by Langmuir-Blodgett films of amphiphilic block copolymers

    Czech Academy of Sciences Publication Activity Database

    Kubies, Dana; Machová, Luďka; Brynda, Eduard; Lukáš, Jaromír; Rypáček, František

    2003-01-01

    Roč. 14, č. 2 (2003), s. 143-149 ISSN 0957-4530 R&D Projects: GA ČR GA203/99/0576 Institutional research plan: CEZ:AV0Z4050913 Keywords : polylactide * Langmuir - Blodgett films * amphiphilic block copolymers Subject RIV: CD - Macromolecular Chemistry Impact factor: 0.930, year: 2003

  9. Fabrication of Propeller-Shaped Supra-amphiphile for Construction of Enzyme-Responsive Fluorescent Vesicles.

    Science.gov (United States)

    Li, Jie; Liu, Kaerdun; Han, Yuchun; Tang, Ben Zhong; Huang, Jianbin; Yan, Yun

    2016-10-04

    Propeller-shaped molecules have been recognized to display fantastic AIE (aggregation induced emission), but they can hardly self-assemble into nanostructures. Herein, we for the first time report that ionic complexation between a water-soluble tetrapheneyl derivative and an enzyme substrate in aqueous media produces a propeller-shaped supra-amphiphile that self-assembles into enzyme responsive fluorescent vesicles. The supra-amphiphile was fabricated upon complexation between a water-soluble propeller-shaped AIE luminogen TPE-BPA and myristoylcholine chloride (MChCl) in aqueous media. MChCl filled in the intramolecular voids of propeller-shaped TPE-BPA upon supra-amphiphile formation, which endows the supra-amphiphile superior self-assembling ability to the component molecules thus leading to the formation of fluorescent vesicles. Because MChCl is the substrate of cholinesterases, the vesicles dissemble in the presence of cholinesterases, and the fluorescent intensity can be correlated to the level of enzymes. The resulting fluorescent vesicles may be used to recognize the site of Alzheimer's disease, to encapsulate the enzyme inhibitor, and to release the inhibitor at the disease site.

  10. Anti-Biofouling Properties of Comblike Block Copolymers with Amphiphilic Side Chains

    International Nuclear Information System (INIS)

    Krishnan, S.; Ayothi, R.; Hexemer, A.; Finlay, J.; Sohn, K.; Perry, R.; Ober, C.; Kramer, E.; Callow, M.

    2006-01-01

    Surfaces of novel block copolymers with amphiphilic side chains were studied for their ability to influence the adhesion of marine organisms. The surface-active polymer, obtained by grafting fluorinated molecules with hydrophobic and hydrophilic blocks to a block copolymer precursor, showed interesting bioadhesion properties. Two different algal species, one of which adhered strongly to hydrophobic surfaces, and the other, to hydrophilic surfaces, showed notably weak adhesion to the amphiphilic surfaces. Both organisms are known to secrete adhesive macromolecules, with apparently different wetting characteristics, to attach to underwater surfaces. The ability of the amphiphilic surface to undergo an environment-dependent transformation in surface chemistry when in contact with the extracellular polymeric substances is a possible reason for its antifouling nature. Near-edge X-ray absorption fine structure spectroscopy (NEXAFS) was used, in a new approach based on angle-resolved X-ray photoelectron spectroscopy (XPS), to determine the variation in chemical composition within the top few nanometers of the surface and also to study the surface segregation of the amphiphilic block. A mathematical model to extract depth-profile information from the normalized NEXAFS partial electron yield is developed

  11. The encapsulation of an amphiphile into polystyrene microspheres of narrow size distribution

    Directory of Open Access Journals (Sweden)

    Pellach Michal

    2011-12-01

    Full Text Available Abstract Encapsulation of compounds into nano- or microsized organic particles of narrow size distribution is of increasing importance in fields of advanced imaging and diagnostic techniques and drug delivery systems. The main technology currently used for encapsulation of molecules within uniform template particles while retaining their size distribution is based on particle swelling methodology, involving penetration of emulsion droplets into the particles. The swelling method, however, is efficient for encapsulation only of hydrophobic compounds within hydrophobic template particles. In order to be encapsulated, the molecules must favor the hydrophobic phase of an organic/aqueous biphasic system, which is not easily achieved for molecules of amphiphilic character. The following work overcomes this difficulty by presenting a new method for encapsulation of amphiphilic molecules within uniform hydrophobic particles. We use hydrogen bonding of acid and base, combined with a pseudo salting out effect, for the entrapment of the amphiphile in the organic phase of a biphasic system. Following the entrapment in the organic phase, we demonstrated, using fluorescein and (antibiotic tetracycline as model molecules, that the swelling method usually used only for hydrophobes can be expanded and applied to amphiphilic molecules.

  12. Novel self-associative and multiphase nanostructured soft carriers based on amphiphilic hyaluronic acid derivatives

    DEFF Research Database (Denmark)

    Eenschooten, Corinne; Vaccaro, Andrea; Delie, Florence

    2012-01-01

    The purpose of the present study was to investigate the physicochemical properties in aqueous media of amphiphilic hyaluronic acid (HA) derivatives obtained by reaction of HA’s hydroxyl groups with octenyl succinic anhydride (OSA). The self-associative properties of the resulting octenyl succinic...

  13. The encapsulation of an amphiphile into polystyrene microspheres of narrow size distribution.

    Science.gov (United States)

    Pellach, Michal; Margel, Shlomo

    2011-12-06

    Encapsulation of compounds into nano- or microsized organic particles of narrow size distribution is of increasing importance in fields of advanced imaging and diagnostic techniques and drug delivery systems. The main technology currently used for encapsulation of molecules within uniform template particles while retaining their size distribution is based on particle swelling methodology, involving penetration of emulsion droplets into the particles. The swelling method, however, is efficient for encapsulation only of hydrophobic compounds within hydrophobic template particles. In order to be encapsulated, the molecules must favor the hydrophobic phase of an organic/aqueous biphasic system, which is not easily achieved for molecules of amphiphilic character.The following work overcomes this difficulty by presenting a new method for encapsulation of amphiphilic molecules within uniform hydrophobic particles. We use hydrogen bonding of acid and base, combined with a pseudo salting out effect, for the entrapment of the amphiphile in the organic phase of a biphasic system. Following the entrapment in the organic phase, we demonstrated, using fluorescein and (antibiotic) tetracycline as model molecules, that the swelling method usually used only for hydrophobes can be expanded and applied to amphiphilic molecules.

  14. Amphiphilic derivatives of (3β,17β)-3-hydroxyandrost-5-ene-17-carboxylic acid

    Czech Academy of Sciences Publication Activity Database

    Özdemir, Zülal; Bildziukevich, Uladzimir; Šaman, David; Havlíček, Libor; Rárová, L.; Navrátilová, L.; Wimmer, Zdeněk

    2017-01-01

    Roč. 128, DEC (2017), s. 58-67 ISSN 0039-128X R&D Projects: GA MŠk LD15012 Institutional support: RVO:61389030 ; RVO:61388963 Keywords : Amphiphile * Antimicrobial activity * Cytotoxicity * Diamine * Polyamine * Steroid Subject RIV: CC - Organic Chemistry; CC - Organic Chemistry (UOCHB-X) OBOR OECD: Organic chemistry Impact factor: 2.282, year: 2016

  15. Self-assembly of aromatic-derivatized amphiphiles: Phenyl, biphenyl, and terphenyl fatty acids and phospholipids

    Energy Technology Data Exchange (ETDEWEB)

    Geiger, H.C.; Perlstein, J.; Lachicotte, R.J.; Wyrozebski, K.; Whitten, D.G. [Univ. of Rochester, NY (United States)]|[Los Alamos National Lab., NM (United States). Chemical Science and Technology Div.

    1999-08-17

    This paper reports the synthesis of a series of amphiphiles (fatty acids and phosphatidylcholine derivatives) containing phenyl, biphenyl, and terphenyl chromophores inserted in the hydrocarbon chain and a study of their self-assembly in Langmuir-Blodgett films and aqueous dispersions. As observed and reported earlier for amphiphiles containing trans-stilbene, styrylthiophene, or azobenzene chromophores, several of the biphenyl and terphenyl derivatives show strong evidence of ground state association to form H aggregates characterized by a blue shift in absorption and a structured, red-shifted fluorescence. The phenyl amphiphiles show different behavior, suggesting that, even for pure films or bilayers, there is very little or no ground state association. For the biphenyl and terphenyl phospholipids, aqueous suspensions obtained by sonication are closed bilayer vesicles similar in size to those formed from the corresponding saturated phospholipids. The overall results of the present study indicate that biphenyl and terphenyl amphiphiles undergo aggregation processes to form compact arrays formally similar to those observed with stilbenen tolan, azobenzene, and squaraine derivatives but that the aromatic-aromatic interactions are considerably weaker than those for the more extended aromatics and lead to less distortion of the assembly structure.

  16. H-aggregation of azobenzene-substituted amphiphiles in vesicular membranes

    NARCIS (Netherlands)

    Kuiper, JM; Engberts, JBFN

    2004-01-01

    Photochemical switching has been studied of double-tailed phosphate amphiphiles containing azobenzene units in both tails in aqueous vesicular dispersions and in mixed vesicular systems with 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC). Since the ease of switching depends on the strength of the

  17. Platform Approach to Produce Polymer Nanoparticles with Modular Functionality from Amphiphilic Block Copolymer Stabilizers

    Science.gov (United States)

    2014-04-01

    Bonilla, A.; Herk, A. M.; Heuts , J. P. A. Preparation of hairy particles and antifouling films using brush-type amphiphilic block copolymer...surfactants in emulsion polymerization. Macromolecules 2010, 43 (6), 2721–2731. 5. Muñoz-Bonilla, A.; Herk, A. M.; Heuts , J. P. A. Adding stimuli

  18. Investigating the Structure of Aggregates of an Amphiphilic Cyanine Dye with Molecular Dynamics Simulations

    NARCIS (Netherlands)

    Haverkort, Frank; Stradomska, Anna; de Vries, Alex H.; Knoester, Jasper

    2013-01-01

    We perform molecular dynamics (MD) simulations of the self-assembly process of pseudoisocyanine dye molecules with amphiphilic substituents (amphi-PIC). The spontaneous aggregation of cyanine molecules into large molecular J-aggregates with optical functionality has drawn attention for many decades

  19. One-pot synthesis of isocyanate and methacrylate multifunctionalized polyisobutylene and polyisobutylene-based amphiphilic networks

    Czech Academy of Sciences Publication Activity Database

    Toman, Luděk; Janata, Miroslav; Spěváček, Jiří; Dvořánková, B.; Látalová, Petra; Vlček, Petr; Sikora, Antonín; Michálek, Jiří; Pekárek, Michal

    2006-01-01

    Roč. 44, č. 9 (2006), s. 2891-2900 ISSN 0887-624X R&D Projects: GA ČR GA203/04/1050 Institutional research plan: CEZ:AV0Z40500505 Keywords : amphiphilic networks * cationic copolymerization * 2-hydroxyethyl methacrylate isobutylene Subject RIV: CD - Macromolecular Chemistry Impact factor: 3.405, year: 2006

  20. Generation dependent mesophase behavior in extended amphiphilic dendrons in the shape of macromolecular dumbbells.

    Science.gov (United States)

    Cho, Byoung-Ki; Jain, Anurag; Gruner, Sol M; Wiesner, Ulrich

    2005-04-28

    Small angle X-ray scattering studies of 2nd and 3rd generation based extended amphiphilic dendrons in the shape of macromolecular dumbbells with identical hydrophilic volume fractions suggest 2-D hexagonal columnar and Pm3n micellar cubic mesophases, respectively, elucidating the role of shape induced interface curvature in mesophase formation.

  1. Influence of corona structure on binding of an ionic surfactant in oppositely charged amphiphilic polyelectrolyte micelles

    Czech Academy of Sciences Publication Activity Database

    Delisavva, F.; Uchman, M.; Škvarla, J.; Wozniak, E.; Pavlova, Ewa; Šlouf, Miroslav; Garamus, V. M.; Procházka, K.; Štěpánek, M.

    2016-01-01

    Roč. 32, č. 16 (2016), s. 4059-4065 ISSN 0743-7463 R&D Projects: GA TA ČR(CZ) TE01020118; GA MŠk(CZ) LO1507 Institutional support: RVO:61389013 Keywords : amphiphilic polymers * polyelectrolyte * corona structure Subject RIV: CD - Macromolecular Chemistry Impact factor: 3.833, year: 2016

  2. Non-amphiphilic carbohydrate liquid crystals containing an intact monosaccharide moiety

    NARCIS (Netherlands)

    Smits, E; Engberts, J.B.F.N.; Kellogg, R.M; van Doren, H.A.

    1995-01-01

    A chiral rigid moiety which forms the basis of a new class of non-amphiphilic carbohydrate liquid crystals has been developed. This moiety contains a fully intact glucopyranose ring embedded in a trans-decalin structure. The original carbohydrate is substituted so that only two hydroxyl groups are

  3. Totally Organic Redox-Active pH-Sensitive Nanoparticles Stabilized by Amphiphilic Aromatic Polyketones

    NARCIS (Netherlands)

    Araya-Hermosilla, Esteban; Catalán-Toledo, José; Muñoz-Suescun, Fabian; Oyarzun-Ampuero, Felipe; Raffa, Patrizio; Polgar, Lorenzo Massimo; Picchioni, Francesco; Moreno-Villoslada, Ignacio

    2018-01-01

    Amphiphilic aromatic polymers have been synthesized by grafting aliphatic polyketones with 4-(aminomethyl)benzoic acid at different molar ratios via the Paal-Knorr reaction. The resulting polymers, showing diketone conversion degree of 16, 37, 53, and 69 %, have been complexed with the redox-active

  4. Synthesis of amphiphilic copolymers by ATRP initiated with a bifunctional initiator containing trichlomethyl groups

    Czech Academy of Sciences Publication Activity Database

    Ritz, Pavel; Látalová, Petra; Janata, Miroslav; Toman, Luděk; Kříž, Jaroslav; Genzer, J.; Vlček, Petr

    2007-01-01

    Roč. 67, č. 10 (2007), s. 1027-1039 ISSN 1381-5148 R&D Projects: GA MŠk 1P05ME753 Institutional research plan: CEZ:AV0Z40500505 Keywords : ATRP * block copolymer * polyhalogenated initiator * amphiphilic copolymer Subject RIV: CD - Macromolecular Chemistry Impact factor: 1.720, year: 2007

  5. Structural properties and elasticity of amphiphilics on water

    Science.gov (United States)

    Daillant, J.; Bosio, L.; Harzallah, B.; Benattar, J. J.

    1991-02-01

    Monolayers of amphiphilic molecules adsorbed at the air-water interface have been studied using X-ray reflectivity. This technique allows an accurate and independent determination of thicknesses (by the measurement of fringes of equal inclination) as well as densities and roughnesses (since this is an absolute intensity measurement); therefore a complete electron density profile can be obtained. The surface roughness is due to thermally excited capillary waves, and is thus related to the dynamics of the interface, which are conditionned by the elastic constants of the layer. The phase diagrams of the C{15}, C{21} and C{29} fatty acids and of the phospholipid L-α-DPPC have been investigated using this method, and an analysis of the phase transitions has been performed. From the structural point of view, a general feature of this class of compounds adsorbed on water is an unchanging aliphatic medium density within the liquid and solid phases. If follows that the pressure vs. film thickness curves mimic the pressure area curves. In particular evidence for the liquid-expanded to liquid-condensed transition is given by an abrupt increase of the aliphatic medium thickness. The data suggest that this transition should involve conformational changes. Furthermore the decrease in molecular area within the liquid condensed phase is revealed by a decreasing molecular tilt angle. The structure of this phase is also shown to be independent of the temperature and of the nature of the polar head-group. A transition to a multilayer structure is observed with the longest chain compound. We show that the dynamics of the interface are consistent in the liquid phases with a simple capillary wave model, with no adjustable parameter. A strong drop in the roughness at the transition to the solid state reveals the onset of a rigidity against bending. The high values of the rigidity modulus obtained (on the order of 100 k_B T) are sensitive to the aliphatic chain length and can be

  6. Photochemical internalisation of a macromolecular protein toxin using a cell penetrating peptide-photosensitiser conjugate.

    Science.gov (United States)

    Wang, Julie T-W; Giuntini, Francesca; Eggleston, Ian M; Bown, Stephen G; MacRobert, Alexander J

    2012-01-30

    Photochemical internalisation (PCI) is a site-specific technique for improving cellular delivery of macromolecular drugs. In this study, a cell penetrating peptide, containing the core HIV-1 Tat 48-57 sequence, conjugated with a porphyrin photosensitiser has been shown to be effective for PCI. Herein we report an investigation of the photophysical and photobiological properties of a water soluble bioconjugate of the cationic Tat peptide with a hydrophobic tetraphenylporphyrin derivative. The cellular uptake and localisation of the amphiphilic bioconjugate was examined in the HN5 human head and neck squamous cell carcinoma cell line. Efficient cellular uptake and localisation in endo/lysosomal vesicles was found using fluorescence detection, and light-induced, rupture of the vesicles resulting in a more diffuse intracellular fluorescence distribution was observed. Conjugation of the Tat sequence with a hydrophobic porphyrin thus enables cellular delivery of an amphiphilic photosensitiser which can then localise in endo/lysosomal membranes, as required for effective PCI treatment. PCI efficacy was tested in combination with a protein toxin, saporin, and a significant reduction in cell viability was measured versus saporin or photosensitiser treatment alone. This study demonstrates that the cell penetrating peptide-photosensitiser bioconjugation strategy is a promising and versatile approach for enhancing the therapeutic potential of bioactive agents through photochemical internalisation. Copyright © 2011 Elsevier B.V. All rights reserved.

  7. A monodisperse transmembrane α-helical peptide barrel

    Science.gov (United States)

    Mahendran, Kozhinjampara R.; Niitsu, Ai; Kong, Lingbing; Thomson, Andrew R.; Sessions, Richard B.; Woolfson, Derek N.; Bayley, Hagan

    2017-05-01

    The fabrication of monodisperse transmembrane barrels formed from short synthetic peptides has not been demonstrated previously. This is in part because of the complexity of the interactions between peptides and lipids within the hydrophobic environment of a membrane. Here we report the formation of a transmembrane pore through the self-assembly of 35 amino acid α-helical peptides. The design of the peptides is based on the C-terminal D4 domain of the Escherichia coli polysaccharide transporter Wza. By using single-channel current recording, we define discrete assembly intermediates and show that the pore is most probably a helix barrel that contains eight D4 peptides arranged in parallel. We also show that the peptide pore is functional and capable of conducting ions and binding blockers. Such α-helix barrels engineered from peptides could find applications in nanopore technologies such as single-molecule sensing and nucleic-acid sequencing.

  8. Systematic discovery of new recognition peptides mediating protein interaction networks

    DEFF Research Database (Denmark)

    Neduva, Victor; Linding, Rune; Su-Angrand, Isabelle

    2005-01-01

    Many aspects of cell signalling, trafficking, and targeting are governed by interactions between globular protein domains and short peptide segments. These domains often bind multiple peptides that share a common sequence pattern, or "linear motif" (e.g., SH3 binding to PxxP). Many domains are kn...

  9. Identification of Cyclin A Binders with a Fluorescent Peptide Sensor.

    Science.gov (United States)

    Pazos, Elena; Mascareñas, José L; Vázquez, M Eugenio

    2016-01-01

    A peptide sensor that integrates the 4-dimethylaminophthalimide (4-DMAP) fluorophore in a short cyclin A binding sequence displays a large fluorescence emission increase upon interacting with the cyclin A Binding Groove (CBG). Competitive displacement assays of this probe allow the straightforward identification of peptides that interact with the CBG, which could potentially block the recognition of CDK/cyclin A kinase substrates.

  10. Cycloaddition in peptides for high-capacity optical storage

    DEFF Research Database (Denmark)

    Lohse, Brian; Berg, Rolf Henrik; Hvilsted, Søren

    2006-01-01

    Photodimerization of chromophores attached to a short peptide chain is investigated for high-capacity optical digital storage with UV lasers. The length and rigidity of the peptide chain assure an optimal distance and orientation of the chromophores for effective photodimerization. Using a theory...

  11. Uniting polypeptides with sequence-designed peptides: synthesis and assembly of poly(gamma-benzyl L-glutamate)-b-coiled-coil peptide copolymers.

    Science.gov (United States)

    Marsden, Hana Robson; Handgraaf, Jan-Willem; Nudelman, Fabio; Sommerdijk, Nico A J M; Kros, Alexander

    2010-02-24

    A new class of peptide has been created, polypeptide-b-designed peptides, which unites the useful qualities of the two constituent peptide types. We demonstrate the synthesis and self-assembly possibilities of this class of peptide chimera with a series of amphiphilic polypeptide-b-designed peptides in which the hydrophobic block is poly(gamma-benzyl l-glutamate) (PBLG) and the hydrophilic block is a coiled-coil forming peptide (denoted E). The synthetic approach was to synthesize the coiled-coil forming peptide on the solid phase, followed by the ring-opening polymerization of gamma-benzyl l-glutamate N-carboxyanhydride, initiated from the N-terminal amine of the peptide E on the solid support. The polypeptide-b-peptide was then cleaved from the resin, requiring no further purification. Peptide E contains 22 amino acids, while the average length of the PBLG block ranged from 36 to 250 residues. This new class of peptide was applied to create a modular system, which relied on juxtaposing the properties of the component peptide types, namely the broad size range and structure-inducing characteristics of the polypeptide PBLG blocks, and the complex functionality of the sequence-designed peptide. Specifically, the different PBLG block lengths could be connected noncovalently with various hydrophilic blocks via the specific coiled-coil folding of E with K or K-poly(ethylene glycol), where K is a peptide of complementary amino acid sequence to E. In this way, nanostructures could be formed in water at neutral pH over the entire compositional range, which has not been demonstrated previously with such large PBLG blocks. It was found that the size, morphology (polymersomes or bicelles), and surface functionality could be specified by combining the appropriate modular building blocks. The self-assembled structures were characterized by dynamic light scattering, circular dichroism, scanning electron microscopy, cryogenic-transmission electron microscopy, fluorescence

  12. PeptideAtlas

    Data.gov (United States)

    U.S. Department of Health & Human Services — PeptideAtlas is a multi-organism, publicly accessible compendium of peptides identified in a large set of tandem mass spectrometry proteomics experiments. Mass...

  13. TNYL peptide functional chitosan-g-stearate conjugate micelles for tumor specific targeting

    Directory of Open Access Journals (Sweden)

    Chen FY

    2014-09-01

    Full Text Available Feng-Ying Chen,1 Jing-Jing Yan,1 Han-Xi Yi,2 Fu-Qiang Hu,2 Yong-Zhong Du,2 Hong Yuan,2 Jian You,2 Meng-Dan Zhao1 1Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 2College of Pharmaceutical Science, Zhejiang University, Hangzhou, People’s Republic of China Abstract: Nowadays, a real challenge in cancer therapy is to design drug delivery systems that can achieve high concentrations of drugs at the target site for improved therapeutic effect with reduced side effects. In this research, we designed and synthesized a homing peptide-(TNYLFSPNGPIA, TNYL modified chitosan-g-stearate (CS polymer micelle (named T-CS for targeting delivery. The peptide displayed specific binding affinity to EphB4 which is a member of the Eph family of receptor tyrosine protein kinases. The amphiphilic polymer T-CS can gather into micelles by themselves in an aqueous environment with a low critical micelle concentration value (91.2 µg/L and nano-scaled size (82.1±2.8 nm. The drug encapsulation efficiency reached 86.43% after loading the hydrophobic drug doxorubicin (DOX. The cytotoxicity of T-CS/DOX against SKOV3 cells was enhanced by approximately 2.3-fold when compared with CS/DOX. The quantitative and qualitative analysis for cellular uptake indicated that TNYL modification can markedly increase cellular internalization in the EphB4-overexpressing SKOV3 cell line, especially with a short incubation time. It is interesting that relatively higher uptake of the T-CS/DOX micelles by SKOV3 cells (positive-EphB4 than A549 cells (negative-EphB4 was observed when the two cells were co-incubated. Furthermore, in vivo distribution experiment using a bilateral-tumor model showed that there was more fluorescence accumulation in the SKOV3 tumor than in the A549 tumor over the whole experiment. These results suggest that TNYL-modified CS micelles may be promising drug carriers as targeting therapy for the EphB4-overexpressing

  14. Designer Natriuretic Peptides

    Science.gov (United States)

    Lee, Candace Y. W.; Lieu, Hsiao; Burnett, John C.

    2011-01-01

    Designer natriuretic peptides (NPs) are novel hybrid peptides that are engineered from the native NPs through addition, deletion, or substitution of amino acid(s) with a goal toward optimization of pharmacological actions while minimizing undesirable effects. In this article, selected peptides that were designed in our laboratory are reviewed, and future directions for research and development of designer NPs are discussed. PMID:19158603

  15. PH dependent adhesive peptides

    Science.gov (United States)

    Tomich, John; Iwamoto, Takeo; Shen, Xinchun; Sun, Xiuzhi Susan

    2010-06-29

    A novel peptide adhesive motif is described that requires no receptor or cross-links to achieve maximal adhesive strength. Several peptides with different degrees of adhesive strength have been designed and synthesized using solid phase chemistries. All peptides contain a common hydrophobic core sequence flanked by positively or negatively charged amino acids sequences.

  16. Antimicrobial Peptides in 2014

    Directory of Open Access Journals (Sweden)

    Guangshun Wang

    2015-03-01

    Full Text Available This article highlights new members, novel mechanisms of action, new functions, and interesting applications of antimicrobial peptides reported in 2014. As of December 2014, over 100 new peptides were registered into the Antimicrobial Peptide Database, increasing the total number of entries to 2493. Unique antimicrobial peptides have been identified from marine bacteria, fungi, and plants. Environmental conditions clearly influence peptide activity or function. Human α-defensin HD-6 is only antimicrobial under reduced conditions. The pH-dependent oligomerization of human cathelicidin LL-37 is linked to double-stranded RNA delivery to endosomes, where the acidic pH triggers the dissociation of the peptide aggregate to release its cargo. Proline-rich peptides, previously known to bind to heat shock proteins, are shown to inhibit protein synthesis. A model antimicrobial peptide is demonstrated to have multiple hits on bacteria, including surface protein delocalization. While cell surface modification to decrease cationic peptide binding is a recognized resistance mechanism for pathogenic bacteria, it is also used as a survival strategy for commensal bacteria. The year 2014 also witnessed continued efforts in exploiting potential applications of antimicrobial peptides. We highlight 3D structure-based design of peptide antimicrobials and vaccines, surface coating, delivery systems, and microbial detection devices involving antimicrobial peptides. The 2014 results also support that combination therapy is preferred over monotherapy in treating biofilms.

  17. Peptide Nucleic Acid Synthons

    DEFF Research Database (Denmark)

    2004-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  18. Peptide-Carrier Conjugation

    DEFF Research Database (Denmark)

    Hansen, Paul Robert

    2015-01-01

    To produce antibodies against synthetic peptides it is necessary to couple them to a protein carrier. This chapter provides a nonspecialist overview of peptide-carrier conjugation. Furthermore, a protocol for coupling cysteine-containing peptides to bovine serum albumin is outlined....

  19. Peptide Nucleic Acids

    DEFF Research Database (Denmark)

    2003-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  20. Peptide Nucleic Acids (PNA)

    DEFF Research Database (Denmark)

    2002-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  1. Peptide Nucleic Acids

    DEFF Research Database (Denmark)

    1998-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  2. Adsorption of phthalic acid esters (PAEs) by amphiphilic polypropylene nonwoven from aqueous solution: the study of hydrophilic and hydrophobic microdomain.

    Science.gov (United States)

    Zhou, Xiangyu; Wei, Junfu; Zhang, Huan; Liu, Kai; Wang, Han

    2014-05-30

    A kind of amphiphilic polypropylene nonwoven with hydrophilic and hydrophobic microdomain was prepared through electron beam induced graft polymerization and subsequent ring opening reaction and then utilized in the adsorption of phthalic acid esters (PAEs). To elucidate the superiority of such amphiphilic microdomain, a unique structure without hydrophilic part was constructed as comparison. In addition, the adsorption behaviors including adsorption kinetics, isotherms and pH effect were systematically investigated. The result indicated that the amphiphilic structure and the synergy between hydrophilic and hydrophobic microdomain could considerably improve the adsorption capacities, rate and affinity. Particularly the existence of hydrophilic microdomain could reduce the diffusion resistance and energy barrier in the adsorption process. These adsorption results showed that the amphiphilic PP nonwoven have the potential to be used in environmental application. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Microspheres for protein delivery prepared from amphiphilic multiblock copolymers. 1. influence of preparation techniques on particle characteristics and protein delivery

    NARCIS (Netherlands)

    Bezemer, J.M.; Radersma, R.; Grijpma, Dirk W.; Dijkstra, Pieter J.; van Blitterswijk, Clemens; Feijen, Jan

    2000-01-01

    The entrapment of lysozyme in amphiphilic multiblock copolymer microspheres by emulsification and subsequent solvent removal processes was studied. The copolymers are composed of hydrophilic poly(ethylene glycol) (PEG) blocks and hydrophobic poly(butylene terephthalate) (PBT) blocks. Direct solvent

  4. The PDB database is a rich source of alpha-helical anti-microbial peptides to combat disease causing pathogens.

    Science.gov (United States)

    Chakraborty, Sandeep; Phu, My; de Morais, Tâmara Prado; Nascimento, Rafael; Goulart, Luiz Ricardo; Rao, Basuthkar J; Asgeirsson, Bjarni; Dandekar, Abhaya M

    2014-01-01

    The therapeutic potential of α-helical anti-microbial peptides (AH-AMP) to combat pathogens is fast gaining prominence. Based on recently published open access software for characterizing α-helical peptides (PAGAL), we elucidate a search methodology (SCALPEL) that leverages the massive structural data pre-existing in the PDB database to obtain AH-AMPs belonging to the host proteome. We provide in vitro validation of SCALPEL on plant pathogens ( Xylella fastidiosa, Xanthomonas arboricola and Liberibacter crescens) by identifying AH-AMPs that mirror the function and properties of cecropin B, a well-studied AH-AMP. The identified peptides include a linear AH-AMP present within the existing structure of phosphoenolpyruvate carboxylase (PPC20), and an AH-AMP mimicing the properties of the two α-helices of cecropin B from chitinase (CHITI25). The minimum inhibitory concentration of these peptides are comparable to that of cecropin B, while anionic peptides used as control failed to show any inhibitory effect on these pathogens. Substitute therapies in place of conventional chemotherapies using membrane permeabilizing peptides like these might also prove effective to target cancer cells. The use of native structures from the same organism could possibly ensure that administration of such peptides will be better tolerated and not elicit an adverse immune response. We suggest a similar approach to target Ebola epitopes, enumerated using PAGAL recently, by selecting suitable peptides from the human proteome, especially in wake of recent reports of cationic amphiphiles inhibiting virus entry and infection.

  5. Pickering stabilized peptide gel particles as tunable microenvironments for biocatalysis.

    Science.gov (United States)

    Scott, Gary; Roy, Sangita; Abul-Haija, Yousef M; Fleming, Scott; Bai, Shuo; Ulijn, Rein V

    2013-11-19

    We demonstrate the preparation of peptide gel microparticles that are emulsified and stabilized by SiO2 nanoparticles. The gels are composed of aromatic peptide amphiphiles 9-fluorenylmethoxycarbonyldiphenylalanine (Fmoc-FF) coassembled with Fmoc-amino acids with different functional groups (S: serine; D: aspartic acid; K: lysine; and Y: tyrosine). The gel phase provides a highly hydrated matrix, and peptide self-assembly endows the matrix with tunable chemical environments which may be exploited to support and stabilize proteins. The use of Pickering emulsion to stabilize these gel particles is advantageous through avoidance of surfactants that may denature proteins. The performance of enzyme lipase B immobilized in pickering/gel microparticles with different chemical functionalities is investigated by studying transesterification in heptane. We show that the use of Pickering particles enhances the performance of the enzyme, which is further improved in gel-phase systems, with hydrophilic environment provided by Fmoc-FF/S giving rise to the best catalytic performance. The combination of a tunable chemical environment in gel phase and Pickering stabilization described here is expected to prove useful for areas where proteins are to be exploited in technological contexts such as biocatalysis and also in other areas where protein performance and activity are important, such as biosensors and bioinspired solar fuel devices.

  6. Photophysical and photochemical studies of a novel amphiphilic zinc phthalocyanine and its interaction with calf thymus DNA

    Science.gov (United States)

    Yuan, Linxin; Gui, Li; Wang, Yue; Zhang, Quanquan; Zhou, Lin; Wei, Shaohua

    2016-04-01

    β-tetra (aminophenoxy) sulfonic substituted zinc phthalocyanines (SNZnPc), a novel amphiphilic zinc phthalocyanine (Pc), was synthesized. The photophysical, photochemical, and photobiology properties were studied. Results indicated that the synthesized SNZnPc has good amphiphilic property and high reactive oxygen species (ROSs) generation ability. Furthermore, SNZnPc has strong affinity to calf thymus DNA (CT-DNA) through intercalation ways and can effectively cleavage CT-DNA after irradiation by light with appropriate wavelength.

  7. Catalytic Y-tailed amphiphilic homopolymers – aqueous nanoreactors for high activity, low loading SCS pincer catalysts

    OpenAIRE

    Patterson, Joseph P.; Cotanda, Pepa; Kelley, Elizabeth G.; Moughton, Adam O.; Lu, Annhelen; Epps, Thomas H.; O’Reilly, Rachel K.

    2013-01-01

    A new amphiphilic homopolymer bearing an SCS pincer palladium complex has been synthesized by reversible addition fragmentation chain transfer polymerization. The amphiphile has been shown to form spherical and worm-like micelles in water by cryogenic transmission electron microscopy and small angle neutron scattering. Segregation of reactive components within the palladium containing core results in increased catalytic activity of the pincer compound compared to small molecule analogues. Thi...

  8. Contribution of Electrostatics in the Fibril Stability of a Model Ionic-Complementary Peptide.

    Science.gov (United States)

    Owczarz, Marta; Casalini, Tommaso; Motta, Anna C; Morbidelli, Massimo; Arosio, Paolo

    2015-12-14

    In this work we quantified the role of electrostatic interactions in the self-assembly of a model amphiphilic peptide (RADA 16-I) into fibrillar structures by a combination of size exclusion chromatography and molecular simulations. For the peptide under investigation, it is found that a net charge of +0.75 represents the ideal condition to promote the formation of regular amyloid fibrils. Lower net charges favor the formation of amorphous precipitates, while larger net charges destabilize the fibrillar aggregates and promote a reversible dissociation of monomers from the ends of the fibrils. By quantifying the dependence of the equilibrium constant of this reversible reaction on the pH value and the peptide net charge, we show that electrostatic interactions contribute largely to the free energy of fibril formation. The addition of both salt and a charged destabilizer (guanidinium hydrochloride) at moderate concentration (0.3-1 M) shifts the monomer-fibril equilibrium toward the fibrillar state. Whereas the first effect can be explained by charge screening of electrostatic repulsion only, the promotion of fibril formation in the presence of guanidinium hydrochloride is also attributed to modifications of the peptide conformation. The results of this work indicate that the global peptide net charge is a key property that correlates well with the fibril stability, although the peptide conformation and the surface charge distribution also contribute to the aggregation propensity.

  9. Adsorption of phthalic acid esters (PAEs) by amphiphilic polypropylene nonwoven from aqueous solution: The study of hydrophilic and hydrophobic microdomain

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Xiangyu [State Key Laboratory of Hollow Fiber Membrane Materials and Processes, Tianjin Polytechnic University, Tianjin 300387 (China); School of Environmental and Chemical Engineering, Tianjin Polytechnic University, Tianjin 300387 (China); Wei, Junfu, E-mail: weijunfu1963@163.com [State Key Laboratory of Hollow Fiber Membrane Materials and Processes, Tianjin Polytechnic University, Tianjin 300387 (China); School of Environmental and Chemical Engineering, Tianjin Polytechnic University, Tianjin 300387 (China); Zhang, Huan; Liu, Kai; Wang, Han [State Key Laboratory of Hollow Fiber Membrane Materials and Processes, Tianjin Polytechnic University, Tianjin 300387 (China); School of Environmental and Chemical Engineering, Tianjin Polytechnic University, Tianjin 300387 (China)

    2014-05-01

    Highlights: • Amphiphilic PP-g-GMA-OA nonwoven was prepared and characterized. • Synergy between hydrophilic and hydrophobic microdomain was elucidated. • The effects of hydrophilic microdomain on diffusion resistance and energy barrier were elucidated. • Adsorbent material with amphiphilic structures showed faster adsorption rate and lager adsorption capacity. - Abstract: A kind of amphiphilic polypropylene nonwoven with hydrophilic and hydrophobic microdomain was prepared through electron beam induced graft polymerization and subsequent ring opening reaction and then utilized in the adsorption of phthalic acid esters (PAEs). To elucidate the superiority of such amphiphilic microdomain, a unique structure without hydrophilic part was constructed as comparison. In addition, the adsorption behaviors including adsorption kinetics, isotherms and pH effect were systematically investigated. The result indicated that the amphiphilic structure and the synergy between hydrophilic and hydrophobic microdomain could considerably improve the adsorption capacities, rate and affinity. Particularly the existence of hydrophilic microdomain could reduce the diffusion resistance and energy barrier in the adsorption process. These adsorption results showed that the amphiphilic PP nonwoven have the potential to be used in environmental application.

  10. Novel amphiphilic poly(dimethylsiloxane) based polyurethane networks tethered with carboxybetaine and their combined antibacterial and anti-adhesive property

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Jingxian; Fu, Yuchen; Zhang, Qinghua, E-mail: qhzhang@zju.edu.cn; Zhan, Xiaoli; Chen, Fengqiu

    2017-08-01

    Highlights: • An amphiphilic poly(dimethylsiloxane) (PDMS) based polyurethane (PU) network tethered with carboxybetaine is prepared. • The surface distribution of PDMS and zwitterionic segments produces an obvious amphiphilic heterogeneous surface. • This designed PDMS-based amphiphilic PU network exhibits combined antibacterial and anti-adhesive properties. - Abstract: The traditional nonfouling materials are powerless against bacterial cells attachment, while the hydrophobic bactericidal surfaces always suffer from nonspecific protein adsorption and dead bacterial cells accumulation. Here, amphiphilic polyurethane (PU) networks modified with poly(dimethylsiloxane) (PDMS) and cationic carboxybetaine diol through simple crosslinking reaction were developed, which had an antibacterial efficiency of 97.7%. Thereafter, the hydrolysis of carboxybetaine ester into zwitterionic groups brought about anti-adhesive properties against bacteria and proteins. The surface chemical composition and wettability performance of the PU network surfaces were investigated by attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS) and contact angle analysis. The surface distribution of PDMS and zwitterionic segments produced an obvious amphiphilic heterogeneous surface, which was demonstrated by atomic force microscopy (AFM). Enzyme-linked immunosorbent assays (ELISA) were used to test the nonspecific protein adsorption behaviors. With the advantages of the transition from excellent bactericidal performance to anti-adhesion and the combination of fouling resistance and fouling release property, the designed PDMS-based amphiphilic PU network shows great application potential in biomedical devices and marine facilities.

  11. Molecular dynamics simulations of membrane deformation induced by amphiphilic helices of Epsin, Sar1p, and Arf1

    Science.gov (United States)

    Li, Zhen-Lu

    2018-03-01

    The N-terminal amphiphilic helices of proteins Epsin, Sar1p, and Arf1 play a critical role in initiating membrane deformation. The interactions of these amphiphilic helices with the lipid membranes are investigated in this study by combining the all-atom and coarse-grained simulations. In the all-atom simulations, the amphiphilic helices of Epsin and Sar1p are found to have a shallower insertion depth into the membrane than the amphiphilic helix of Arf1, but remarkably, the amphiphilic helices of Epsin and Sar1p induce higher asymmetry in the lipid packing between the two monolayers of the membrane. The insertion depth of amphiphilic helix into the membrane is determined not only by the overall hydrophobicity but also by the specific distributions of polar and non-polar residues along the helix. To directly compare their ability to deform the membrane, the coarse-grained simulations are performed to investigate the membrane deformation under the insertion of multiple helices. Project supported by the National Natural Science Foundation of China (Grant Nos. 91427302 and 11474155).

  12. Enhancing the protein resistance of silicone via surface-restructuring PEO-silane amphiphiles with variable PEO length.

    Science.gov (United States)

    Rufin, M A; Gruetzner, J A; Hurley, M J; Hawkins, M L; Raymond, E S; Raymond, J E; Grunlan, M A

    2015-04-14

    Silicones with superior protein resistance were produced by bulk-modification with poly(ethylene oxide) (PEO)-silane amphiphiles that demonstrated a higher capacity to restructure to the surface-water interface versus conventional non-amphiphilic PEO-silanes. The PEO-silane amphiphiles were prepared with a single siloxane tether length but variable PEO segment lengths: α-(EtO) 3 Si(CH 2 ) 2 -oligodimethylsiloxane 13 - block -poly(ethylene oxide) n -OCH 3 ( n = 3, 8, and 16). Conventional PEO-silane analogues ( n = 3, 8 and 16) as well as a siloxane tether-silane (i.e. no PEO segment) were prepared as controls. When surface-grafted onto silicon wafer, PEO-silane amphiphiles produced surfaces that were more hydrophobic and thus more adherent towards fibrinogen versus the corresponding PEO-silane. However, when blended into a silicone, PEO-silane amphiphiles exhibited rapid restructuring to the surface-water interface and excellent protein resistance whereas the PEO-silanes did not. Silicones modified with PEO-silane amphiphiles of PEO segment lengths n = 8 and 16 achieved the highest protein resistance.

  13. Adsorption of phthalic acid esters (PAEs) by amphiphilic polypropylene nonwoven from aqueous solution: The study of hydrophilic and hydrophobic microdomain

    International Nuclear Information System (INIS)

    Zhou, Xiangyu; Wei, Junfu; Zhang, Huan; Liu, Kai; Wang, Han

    2014-01-01

    Highlights: • Amphiphilic PP-g-GMA-OA nonwoven was prepared and characterized. • Synergy between hydrophilic and hydrophobic microdomain was elucidated. • The effects of hydrophilic microdomain on diffusion resistance and energy barrier were elucidated. • Adsorbent material with amphiphilic structures showed faster adsorption rate and lager adsorption capacity. - Abstract: A kind of amphiphilic polypropylene nonwoven with hydrophilic and hydrophobic microdomain was prepared through electron beam induced graft polymerization and subsequent ring opening reaction and then utilized in the adsorption of phthalic acid esters (PAEs). To elucidate the superiority of such amphiphilic microdomain, a unique structure without hydrophilic part was constructed as comparison. In addition, the adsorption behaviors including adsorption kinetics, isotherms and pH effect were systematically investigated. The result indicated that the amphiphilic structure and the synergy between hydrophilic and hydrophobic microdomain could considerably improve the adsorption capacities, rate and affinity. Particularly the existence of hydrophilic microdomain could reduce the diffusion resistance and energy barrier in the adsorption process. These adsorption results showed that the amphiphilic PP nonwoven have the potential to be used in environmental application

  14. Acylation of Therapeutic Peptides

    DEFF Research Database (Denmark)

    Trier, Sofie; Henriksen, Jonas Rosager; Jensen, Simon Bjerregaard

    to the harsh and selective gastrointestinal system, and development has lacked far behind injection therapy. Peptide acylation is a powerful tool to alter the pharmacokinetics, biophysical properties and chemical stability of injectable peptide drugs, primarily used to prolong blood circulation....... This work aims to characterize acylated analogues of two therapeutic peptides by systematically increasing acyl chain length in order to elucidate its influence on membrane interaction and intestinal cell translocation in vitro. The studied peptides are the 33 amino acid Glucagon-like peptide-2 (GLP-2...... peptides can increase in vitro intestinal permeability, modestly for GLP-2 and drastically for sCT, and might benefit oral delivery. GLP-2 results provide a well-founded predictive power for future peptide analogues, whereas sCT results hold great promise for future analogues, albeit with a larger...

  15. Bioprinting synthetic self-assembling peptide hydrogels for biomedical applications

    International Nuclear Information System (INIS)

    Loo, Yihua; Hauser, Charlotte A E

    2016-01-01

    Three-dimensional (3D) bioprinting is a disruptive technology for creating organotypic constructs for high-throughput screening and regenerative medicine. One major challenge is the lack of suitable bioinks. Short synthetic self-assembling peptides are ideal candidates. Several classes of peptides self-assemble into nanofibrous hydrogels resembling the native extracellular matrix. This is a conducive microenvironment for maintaining cell survival and physiological function. Many peptides also demonstrate stimuli-responsive gelation and tuneable mechanical properties, which facilitates extrusion before dispensing and maintains the shape fidelity of the printed construct in aqueous media. The inherent biocompatibility and biodegradability bodes well for in vivo applications as implantable tissues and drug delivery matrices, while their short length and ease of functionalization facilitates synthesis and customization. By applying self-assembling peptide inks to bioprinting, the dynamic complexity of biological tissue can be recreated, thereby advancing current biomedical applications of peptide hydrogel scaffolds. (paper)

  16. Evolving the use of peptides as biomaterials components

    Science.gov (United States)

    Collier, Joel H.; Segura, Tatiana

    2012-01-01

    This manuscript is part of a debate on the statement that “the use of short synthetic adhesion peptides, like RGD, is the best approach in the design of biomaterials that guide cell behavior for regenerative medicine and tissue engineering”. We take the position that although there are some acknowledged disadvantages of using short peptide ligands within biomaterials, it is not necessary to discard the notion of using peptides within biomaterials entirely, but rather to reinvent and evolve their use. Peptides possess advantageous chemical definition, access to non-native chemistries, amenability to de novo design, and applicability within parallel approaches. Biomaterials development programs that require such aspects may benefit from a peptide-based strategy. PMID:21515167

  17. Short philtrum

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003302.htm Short philtrum To use the sharing features on this page, please enable JavaScript. A short philtrum is a shorter than normal distance between ...

  18. A theoretical study of colloidal forces near an amphiphilic polymer brush

    Science.gov (United States)

    Wu, Jianzhong

    2011-03-01

    Polymer-based ``non-stick'' coatings are promising as the next generation of effective, environmentally-friendly marine antifouling systems that minimize nonspecific adsorption of extracellular polymeric substances (EPS). However, design and development of such systems are impeded by the poor knowledge of polymer-mediated interactions of biomacromolecules with the protected substrate. In this work, a polymer density functional theory (DFT) is used to predict the potential of mean force between spherical biomacromolecules and amphiphilic copolymer brushes within a coarse-grained model that captures essential nonspecific interactions such as the molecular excluded volume effects and the hydrophobic energies. The relevance of theoretical results for practical control of the EPS adsorption is discussed in terms of the efficiency of different brush configurations to prevent biofouling. It is shown that the most effective antifouling surface may be accomplished by using amphiphilic brushes with a long hydrophilic backbone and a hydrophobic end at moderate grafting density.

  19. Efficient size control of amphiphilic cyclodextrin nanoparticles through a statistical mixture design methodology.

    Science.gov (United States)

    Choisnard, Luc; Géze, Annabelle; Bigan, Muriel; Putaux, Jean-Luc; Wouessidjewe, Denis

    2005-12-06

    the aim of the study was to investigate size control of amphiphilic beta-cyclodextrin nanoparticles obtained by solvent displacement technique. An experimental design methodology for mixture design was undertaken using D-optimal approach with the following technique variables: water fraction X1 (40-70% v/v), acetone fraction X2 (0-60% v/v) and ethanol fraction X3 (0-60% v/v). The resulting quadratic model obtained after logarithmic transformation of data and partial least-square regression was statistically validated and experimentally checked. Also, the morphology of the colloidal nanoparticles from selected experiments was observed by cryo-transmission electron microscopy. This experimental design approach allowed to produce interesting amphiphilic beta-cyclodextrin nanoparticles with a predicted mean size varying from 60 to 400 nm.

  20. Amphiphilic block copolymers as efficiency boosters in microemulsions a SANS investigation of the role of polymers

    CERN Document Server

    Endo, H; Mihailescu, M; Monkenbusch, M; Gompper, G; Richter, D; Jakobs, B; Sottmann, T; Strey, R

    2002-01-01

    The effect of amphiphilic block copolymers on ternary microemulsions (water, oil and non-ionic surfactant) is investigated. Small amounts of PEP-PEO block copolymer lead to a dramatic expansion of the one-phase region where water and oil can be solubilized by the mediation of surfactant molecules. Small-angle neutron-scattering experiments employing a high-precision two-dimensional contrast-variation technique demonstrate that the polymer is distributed uniformly on the surfactant membrane, where it modifies the membrane curvature elasticity. Furthermore, a new approach to determine the bending rigidity of an amphiphilic membrane is proposed, which is precise enough to measure the logarithmic scale dependence of the bending rigidity and its universal prefactor in bicontinuous microemulsions. (orig.)

  1. Synthesis of an amphiphilic dendrimer-like block copolymer and its application on drug delivery

    KAUST Repository

    Wang, Shuaipeng

    2014-10-27

    Dendrimer-like amphiphilic copolymer is a kind of three-dimensional spherical structure polymer. An amphiphilic dendrimer-like diblock copolymer, PEEGE-G2-b-PEO(OH)12, constituted of a hydrophobic poly(ethoxyethyl glycidol ether) inner core and a hydrophilic poly(ethylene oxide) outer layer, has been successfully synthesized by the living anionic ring-opening polymerization method. The intermediates and targeted products were characterized with 1H NMR spectroscopy and gel permeation chromatography. The application on drug delivery of dendrimer-like diblock copolymer PEEGE-G2-b-PEO(OH)12 using DOX as a model drug was also studied. The drug loading content and encapsulation efficiency were found at 13.07% and 45.75%, respectively. In vitro release experiment results indicated that the drug-loaded micelles exhibited a sustained release behavior under acidic media.

  2. Synthesis of amphiphilic aminated inulin via 'click chemistry' and evaluation for its antibacterial activity.

    Science.gov (United States)

    Dong, Fang; Zhang, Jun; Yu, Chunwei; Li, Qing; Ren, Jianming; Wang, Gang; Gu, Guodong; Guo, Zhanyong

    2014-09-15

    Inulins are a group of abundant, water-soluble, renewable polysaccharides, which exhibit attractive bioactivities and natural properties. Improvement such as chemical modification of inulin is often performed prior to further utilization. We hereby presented a method to modify inulin at its primary hydroxyls to synthesize amphiphilic aminated inulin via 'click chemistry' to facilitate its chemical manipulation. Additionally, its antibacterial property against Staphylococcus aureus (S. aureus) was also evaluated and the best inhibitory index against S. aureus was 58% at 1mg/mL. As the amphiphilic aminated inulin is easy to prepare and exhibits improved bioactivity, this material may represent as an attractive new platform for chemical modifications of inulin. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Terpene and dextran renewable resources for the synthesis of amphiphilic biopolymers.

    Science.gov (United States)

    Alvès, Marie-Hélène; Sfeir, Huda; Tranchant, Jean-François; Gombart, Emilie; Sagorin, Gilles; Caillol, Sylvain; Billon, Laurent; Save, Maud

    2014-01-13

    The present work shows the synthesis of amphiphilic polymers based on the hydrophilic dextran and the hydrophobic terpenes as renewable resources. The first step concerns the synthesis of functional terpene molecules by thiol-ene addition chemistry involving amino or carboxylic acid thiols and dihydromyrcenol terpene. The terpene-modified polysaccharides were subsequently synthesized by coupling the functional terpenes with dextran. A reductive amination step produced terpene end-modified dextran with 94% of functionalization, while the esterification step produced three terpene-grafted dextrans with a number of terpene units per dextran of 1, 5, and 10. The amphiphilic renewable grafted polymers were tested as emulsifiers for the stabilization of liquid miniemulsion of terpene droplets dispersed in an aqueous phase. The average hydrodynamic diameter of the stable droplets was observed at about 330 nm.

  4. Reverse self-assemblies based on amphiphilic polyphosphazenes for encapsulation of water-soluble molecules

    Science.gov (United States)

    Qiu, Liyan; Zhang, Jianxiang; Yan, Meiqiu; Jin, Yi; Zhu, Kangjie

    2007-11-01

    A novel series of amphiphilic polyphosphazenes (PNIPAm/AA-PPP) containing hydrophilic oligo-(N-isopropylacrylamide) (oligo-NIPAm) and various hydrophobic aliphatic amines as co-substitutes was synthesized via a two-step substitution reaction. The extraction and solubilization of water-soluble substances such as fluorescein sodium and trypan blue from an aqueous phase into the chloroform phase were supposed to result from the formation of polyphosphazene reverse self-assemblies in the organic phase. A field emission scanning electronic microscope was adopted to characterize the morphology of reverse assemblies in chloroform. Additionally, a significant improvement of encapsulation and release profiles of water-soluble substances was found for poly(lactic-co-glycolic acid) (PLGA) microparticles in the presence of amphiphilic copolymers, which was associated with the chemical structure of copolymers as well as the content of copolymer in the microparticles.

  5. Polyaniline Nanofibers: Their Amphiphilicity and Uses for Pickering Emulsions and On-Demand Emulsion Separation.

    Science.gov (United States)

    Zhou, Ping; Li, Jing; Yang, Wenwen; Zhu, Lihua; Tang, Heqing

    2018-02-27

    The wetting property of nanomaterials is of great importance to both fundamental understanding and potential applications. However, the study on the intrinsic wetting property of nanomaterials is interfered by organic capping agents, which are often used to lower the surface energy of nanomaterials and avoid their irreversible agglomeration. In this work, the wetting property of the nanostructured polyaniline that requires no organic capping agents is investigated. Compared to hydrophilic granular particulates, polyaniline nanofibers are amphiphilic and have an excellent capability of creating Pickering emulsions at a wide range of pH. It is suggested that polyaniline nanofibers can be easily wetted by water and oil. Furthermore, the amphiphilic polyaniline nanofibers as building blocks can be used to construct filtration membranes with a small pore size. The wetting layer of the continuous phase of emulsions in the porous nanochannels efficiently prevents the permeation of the dispersed phase, realizing high-efficiency on-demand emulsion separation.

  6. Synthesis, Characterization, and Aqueous Lubricating Properties of Amphiphilic Graft Copolymers Comprising 2-Methoxyethyl Acrylate

    DEFF Research Database (Denmark)

    Javakhishvili, Irakli; Røn, Troels; Jankova Atanasova, Katja

    2014-01-01

    Amphiphilic anionic and cationic graft copolymers possessing poly(2-hydroxyethyl methacrylate) (PHEMA) backbone and poly(methacrylic acid), poly(2-methoxyethyl acrylate-co-methacrylic acid), and poly(2-methoxyethyl acrylate-co-2-(dimethylamino)ethyl methacrylate) grafts are constructed by merging...... of the corresponding monomers followed by deblocking reaction leads to well-defined amphiphiles with narrow molecular weight distributions (PDI ≤ 1.29) and varying content of methacrylic acid. The graft copolymers showed effective surface adsorption and lubrication for self-mated poly(dimethylsiloxane) (PDMS) contacts...... in physiological salt concentration. This is indebted from “dilution” of the charges along the grafted chains by balancing neutral/charged repeating units to minimize the accumulated charge repulsion on neutral surface. Improved lubricating properties of the graft copolymers compared to the block copolymer...

  7. Acute effects of continuous infusions of glucagon-like peptide (GLP)-1, GLP-2 and the combination (GLP-1+GLP-2) on intestinal absorption in short bowel syndrome (SBS) patients. A placebo-controlled study

    DEFF Research Database (Denmark)

    Madsen, K B; Askov-Hansen, C; Naimi, R M

    2013-01-01

    The ileocolonic brake is impaired in short bowel syndrome (SBS) patients with distal bowel resections. An attenuated meal-stimulated hormone secretion may cause gastric hypersecretion, rapid gastric and intestinal transit and a poor adaptation. Attempting to restore this ileocolonic brake...

  8. Amphiphilic Cellulose Ethers Designed for Amorphous Solid Dispersion via Olefin Cross-Metathesis.

    Science.gov (United States)

    Dong, Yifan; Mosquera-Giraldo, Laura I; Taylor, Lynne S; Edgar, Kevin J

    2016-02-08

    The design of cellulose ether-based amphiphiles has been difficult and limited because of the harsh conditions typically required for appending ether moieties to cellulose. Olefin cross-metathesis recently has been shown to be a valuable approach for appending a variety of functional groups to cellulose ethers and esters, provided that an olefin handle for metathesis can be attached. This synthetic pathway gives access to these functional derivatives under very mild conditions and at high efficiency. Modification of ethyl cellulose by metathesis to prepare useful derivatives, for example, for solubility and bioavailability enhancement of drugs by amorphous solid dispersion (ASD), has been limited by the low DS(OH) of commercial ethyl cellulose derivatives. This is problematic because ethyl cellulose is otherwise a very attractive substrate for synthesis of amphiphilic derivatives by olefin metathesis. Herein we explore two methods for opening up this design space for ether-based amphiphiles, for example, permitting synthesis of more hydrophilic derivatives. One approach is to start with the more hydrophilic commercial methyl cellulose, which contains much higher DS(OH) and therefore is better suited for introduction of high DS of olefin metathesis "handles". In another approach, we explored a homogeneous one-pot synthesis methodology from cellulose, where controlled DS of ethyl groups was introduced at the same time as the ω-unsaturated alkyl groups, thereby permitting complete control of DS(OH), DS(Et), and ultimately DS of the functional group added by metathesis. We describe the functionalized derivatives available by these successful approaches. In addition, we explore new methods for reduction of the unsaturation in initial metathesis products to provide robust methods for enhancing product stability against further radical-catalyzed reactions. We demonstrate initial evidence that the products show strong promise as amphiphilic matrix polymers for amorphous

  9. Immunochemically identical hydrophilic and amphiphilic forms of the bovine adrenomedullary dopamine beta-hydroxylase

    DEFF Research Database (Denmark)

    Bjerrum, Ole Jannik; Helle, K B; Bock, Elisabeth Marianne

    1979-01-01

    . The dopamine beta-hydroxylases of the buffer and membrane fractions were antigenically identical, but differed in their amphiphilicity, as demonstrated by the change in precipitation patterns on removal of Triton X-100 from the gel, on charge-shift crossed immunoelectrophoresis and on crossed hydrophobic...... interaction immunoelectrophoresis with phenyl-Sepharose. Furthermore, immunoelectrophoretic analysis in the presence of Triton X-100 plus the cationic detergent cetyltrimethylammonium bromide indicates additional heterogeneity of the membrane-bound dopamine-beta-hydroxylase. By limited proteolysis...

  10. Protein resistance efficacy of PEO-silane amphiphiles: Dependence on PEO-segment length and concentration.

    Science.gov (United States)

    Rufin, Marc A; Barry, Mikayla E; Adair, Paige A; Hawkins, Melissa L; Raymond, Jeffery E; Grunlan, Melissa A

    2016-09-01

    In contrast to modification with conventional PEO-silanes (i.e. no siloxane tether), silicones with dramatically enhanced protein resistance have been previously achieved via bulk-modification with poly(ethylene oxide) (PEO)-silane amphiphiles α-(EtO)3Si(CH2)2-oligodimethylsiloxane13-block-PEOn-OCH3 when n=8 and 16 but not when n=3. In this work, their efficacy was evaluated in terms of optimal PEO-segment length and minimum concentration required in silicone. For each PEO-silane amphiphile (n=3, 8, and 16), five concentrations (5, 10, 25, 50, and 100μmol per 1g silicone) were evaluated. Efficacy was quantified in terms of the modified silicones' abilities to undergo rapid, water-driven surface restructuring to form hydrophilic surfaces as well as resistance to fibrinogen adsorption. Only n=8 and 16 were effective, with a lower minimum concentration in silicone required for n=8 (10μmol per 1g silicone) versus n=16 (25μmol per 1g silicone). Silicone is commonly used for implantable medical devices, but its hydrophobic surface promotes protein adsorption which leads to thrombosis and infection. Typical methods to incorporate poly(ethylene oxide) (PEO) into silicones have not been effective due to the poor migration of PEO to the surface-biological interface. In this work, PEO-silane amphiphiles - comprised of a siloxane tether (m=13) and variable PEO segment lengths (n=3, 8, 16) - were blended into silicone to improve its protein resistance. The efficacy of the amphiphiles was determined to be dependent on PEO length. With the intermediate PEO length (n=8), water-driven surface restructuring and resulting protein resistance was achieved with a concentration of only 1.7wt%. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  11. Recursive Alterations of the Relationship between Simple Membrane Geometry and Insertion of Amphiphilic Motifs

    DEFF Research Database (Denmark)

    Madsen, Kenneth Lindegaard; Herlo, Rasmus

    2017-01-01

    The shape and composition of a membrane directly regulate the localization, activity, and signaling properties of membrane associated proteins. Proteins that both sense and generate membrane curvature, e.g., through amphiphilic insertion motifs, potentially engage in recursive binding dynamics......, where the recruitment of the protein itself changes the properties of the membrane substrate. Simple geometric models of membrane curvature interactions already provide prediction tools for experimental observations, however these models are treating curvature sensing and generation as separated...

  12. Small yet effective: The Ethylene-responsive element binding factor-associated Amphiphilic Repression (EAR) motif

    OpenAIRE

    Kagale, Sateesh; Rozwadowski, Kevin

    2010-01-01

    The Ethylene-responsive element binding factor-associated Amphiphilic Repression (EAR) motif is a small yet distinct regulatory motif that is conserved in many plant transcriptional regulator (TR) proteins associated with diverse biological functions. We have previously established a list of high-confidence Arabidopsis EAR repressors, the EAR repressome, comprising 219 TRs belonging to 21 different TR families. This class of proteins and the sequence context of the EAR motif exhibited a high ...

  13. Vortex-Induced Alignment of a Water Soluble Supramolecular Nanofiber Composed of an Amphiphilic Dendrimer

    Directory of Open Access Journals (Sweden)

    Akihiko Tsuda

    2013-06-01

    Full Text Available We have synthesized a novel amphiphilic naphthalene imide bearing a cationic dendrimer wedge (NID. NID molecules in water self-assemble to form a two-dimensional ribbon, which further coils to give a linear supramolecular nanofiber. The sample solution showed linear dichroism (LD upon stirring of the solution, where NID nanofibers dominantly align at the center of vortex by hydrodynamic interaction with the downward torsional flows.

  14. Cell Penetrating Peptides and Cationic Antibacterial Peptides

    Science.gov (United States)

    Rodriguez Plaza, Jonathan G.; Morales-Nava, Rosmarbel; Diener, Christian; Schreiber, Gabriele; Gonzalez, Zyanya D.; Lara Ortiz, Maria Teresa; Ortega Blake, Ivan; Pantoja, Omar; Volkmer, Rudolf; Klipp, Edda; Herrmann, Andreas; Del Rio, Gabriel

    2014-01-01

    Cell penetrating peptides (CPP) and cationic antibacterial peptides (CAP) have similar physicochemical properties and yet it is not understood how such similar peptides display different activities. To address this question, we used Iztli peptide 1 (IP-1) because it has both CPP and CAP activities. Combining experimental and computational modeling of the internalization of IP-1, we show it is not internalized by receptor-mediated endocytosis, yet it permeates into many different cell types, including fungi and human cells. We also show that IP-1 makes pores in the presence of high electrical potential at the membrane, such as those found in bacteria and mitochondria. These results provide the basis to understand the functional redundancy of CPPs and CAPs. PMID:24706763

  15. Nanoparticles containing octreotide peptides and gadolinium complexes for MRI applications.

    Science.gov (United States)

    Accardo, Antonella; Morisco, Anna; Gianolio, Eliana; Tesauro, Diego; Mangiapia, Gaetano; Radulescu, Aurel; Brandt, Astrid; Morelli, Giancarlo

    2011-02-01

    New mixed nanoparticles were obtained by self-aggregation of two amphiplic monomers. The first monomer (C18)(2) L5-Oct contains two C18 hydrophobic moieties bound to the N-terminus of the cyclic peptide octreotide, and spaced from the bioactive peptide by five units of dioxoethylene linkers. The second monomer, (C18)(2) DTPAGlu, (C18)(2) DTPA or (C18)(2) DOTA, and the corresponding Gd(III) complexes, contains two C18 hydrophobic moieties bound through a lysine residue to different polyamino-polycarboxy ligands: DTPAGlu, DTPA or DOTA. Mixed aggregates have been obtained and structurally characterized by small angle neutron scattering (SANS) techniques and for their relaxometric behavior. According to a decrease of negative charges in the surfactant head-group, a total or a partial micelle-to-vesicle transition is observed by passing from (C18)(2) DTPAGlu to (C18)(2) DOTA. The thicknesses of the bilayers are substantially constant, around 50 Å, in the analyzed systems. Moreover, the mixed aggregates, in which a small amount of amphiphilic octreotide monomer (C18)(2) L5-Oct (10% mol/mol) was inserted, do not differ significantly from the respective self-assembled systems. Fluorescence emission of tryptophan residue at 340 nm indicates low mobility of water molecules at the peptide surface. The proton relaxivity of mixed aggregates based on (C18)(2) DTPAGlu(Gd), (C18)(2) DTPA(Gd) and (C18)(2) DOTA(Gd) resulted to be 17.6, 15.2 and 10.0 mM(-1) s(-1) (at 20 MHz and 298K), respectively. The decrease in the relaxivity values can be ascribed to the increase in τ(M) (81, 205 and 750 ns). The presence of amphiphilic octreotide monomer exposed on mixed aggregate surface gives the entire nanoparticles a potential binding selectivity toward somatostatin sstr2 receptor subtype, and these systems could act as MRI target-specific contrast agent. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd.

  16. Amphiphilic carbon dots for sensitive detection, intracellular imaging of Al{sup 3+}

    Energy Technology Data Exchange (ETDEWEB)

    Kong, Depeng [State Key Laboratory of Separation Membranes and Membrane Processes, School of Environmental and Chemical Engineering, Tianjin Polytechnic University, Tianjin 300387 (China); Yan, Fanyong, E-mail: yanfanyong@tjpu.edu.cn [State Key Laboratory of Separation Membranes and Membrane Processes, School of Environmental and Chemical Engineering, Tianjin Polytechnic University, Tianjin 300387 (China); Luo, Yunmei [Department of Pharmacology/Key Laboratory for Basic Pharmacology of Ministry of Education, Zunyi Medical College, Guizhou 563000 (China); Ye, Qianghua; Zhou, Siyushan [State Key Laboratory of Separation Membranes and Membrane Processes, School of Environmental and Chemical Engineering, Tianjin Polytechnic University, Tianjin 300387 (China); Chen, Li, E-mail: Chenlis@tjpu.edu.cn [State Key Laboratory of Separation Membranes and Membrane Processes, School of Environmental and Chemical Engineering, Tianjin Polytechnic University, Tianjin 300387 (China)

    2017-02-08

    In this paper, a simple and effective method was designed to synthesize hydrophobic carbon dots. Subsequently, amphiphilic fluorescent carbon dots (A-CDs) were synthesized by further surface modification. The result A-CDs show excellent optical properties with a quantum yield of 16.9%. It was interestingly found that morin (MR) and its fluorescent metal-ion complex (MR-Al{sup 3+}) can successfully coordinate on the surface of A-CDs, the emission of A-CDs completely overlapped the absorption peak of MR-Al{sup 3+}. Thus, the prepared A-CDs can be used as an effective fluorescent probe for Al{sup 3+} based on a fluorescence resonance energy transfer process. The sensing platform can realize real-time detection of Al{sup 3+} within 0.5 min. The fluorescence signals of the system were linearly correlated with the concentration of Al{sup 3+} over a range of 8–20 μM, with a detection limit of 0.113 μM. The method was also successfully applied to image the distribution of Al{sup 3+} in Human Umbilical Vein Endothelial Cells. - Highlights: • Amphiphilic carbon dots were obtained by simply modifying hydrophobic carbon dots. • Amphiphilic carbon dots/morin-Al{sup 3+} was used as a selective turn-on probe for Al{sup 3+}. • The method was employed to intracellular imaging Al{sup 3+} in living cells.

  17. Beyond amphiphiles: coarse-grained simulations of star-polyphile liquid crystalline assemblies.

    Science.gov (United States)

    Kirkensgaard, Jacob Judas Kain; Hyde, Stephen

    2009-03-28

    We have simulated the self-assembly of a novel class of three-arm molecules, ABC star-architecture polyphiles, using coarse-grained bead simulations. A number of topologically complex liquid crystalline mesostructures arise that can be related to the better-known bicontinuous mesophases of lyotropic amphiphilic systems. The simulations reveal 3D self-assemblies whose structural variations follow those expected assuming a simple steric molecular packing model as a function of star polyphile splay and relative volumes of each arm in the polyphile. The splay of each arm, characterised by the 3D wedge-shape emanating from the core of each molecule to its exterior induces torsion of the interfaces along the triple lines, whereas differences in the relative volumes of arms induce curvature of the triple lines. Three distinct mesostructures are described, characterised by their micro-domain topologies, which are unknown in simpler amphiphilic systems, but resemble in some respects bicontinuous mesophases. These three- (or more) arm polyphilic systems offer an interesting extension to the better-known self-assembly of (two-arm) amphiphiles in solution.

  18. Morphological Evolution of Self-Assembled Structures Induced by the Molecular Architecture of Supra-Amphiphiles.

    Science.gov (United States)

    Wang, Juan; Li, Boxuan; Wang, Xing; Yang, Fei; Shen, Hong; Wu, Decheng

    2016-12-27

    A series of telechelic supramolecular amphiphiles [POSS-Azo 8 @(β-CD-PDMAEMA) 1→8 ] was accomplished by orthogonally coupling the multiarm host polymer β-cyclodextrin-poly(dimethylaminoethyl methacrylate) (β-CD-PDMAEMA) with an octatelechelic guest molecule azobenzene modified-polyhedral oligomeric silsesquioxanes (POSS-Azo 8 ) under different host-guest ratios. These telechelic supramolecular amphiphiles possess a rigid core and flexible corona. Increasing the multiarm host polymer coupled onto the rigid POSS core made the molecular architecture tend to be symmetrical and spherical. POSS-Azo 8 @[β-CD-PDMAEMA] 1→8 could self-assemble into diverse morphologies evolving from spherical micelles, wormlike micelles, and branched aggregates to bowl-shaped vesicles. Distinct from the traditional linear amphiphilic polymers, we discovered that the self-assembly of POSS-Azo 8 @[β-CD-PDMAEMA] 1→8 was dominantly regulated by their molecular architectures instead of hydrophilicity, which has also been verified using computer simulation results.

  19. Physical deposition behavior of stiff amphiphilic polyelectrolytes in an external electric field

    Science.gov (United States)

    Hu, Dongmei; Zuo, Chuncheng; Cao, Qianqian; Chen, Hongli

    2017-08-01

    Coarse-grained molecular dynamics simulations are conducted to study the physical deposition behavior of stiff amphiphilic polyelectrolytes (APEs) in an external electric field. The effects of chain stiffness, the charge distribution of a hydrophilic block, and electric field strength are investigated. Amphiphilic multilayers, which consist of a monolayer of adsorbed hydrophilic monomers (HLMs), a hydrophobic layer, and another hydrophilic layer, are formed in a selective solvent. All cases exhibit locally ordered hydrophilic monolayers. Two kinds of hydrophobic micelles are distinguished based on local structures. Stripe and network hydrophobic patterns are formed in individual cases. Increasing the chain stiffness decreases the thickness of the deposited layer, the lateral size of the hydrophobic micelles, and the amount of deposition. Increasing the number of positively charged HLMs in a single chain has the same effect as increasing chain stiffness. Moreover, when applied normally to the substrate, the electric field compresses the deposited structures and increases the amount of deposition by pulling more PEs toward the substrate. A stronger electric field also facilitates the formation of a thinner and more ordered hydrophilic adsorption layer. These estimates help us explore how to tailor patterned nano-surfaces, nano-interfaces, or amphiphilic nanostructures by physically depositing semi-flexible APEs which is of crucial importance in physical sciences, life sciences and nanotechnology.

  20. Cylindrical micelles of a POSS amphiphilic dendrimer as nano-reactors for polymerization.

    Science.gov (United States)

    Weng, Jing-Ting; Yeh, Tso-Fan; Samuel, Ashok Zachariah; Huang, Yi-Fan; Sie, Jyun-Hao; Wu, Kuan-Yi; Peng, Chi-How; Hamaguchi, Hiro-O; Wang, Chien-Lung

    2018-02-15

    A low generation amphiphilic dendrimer, POSS-AD, which has a POSS core and eight amphiphilic arms, was synthesized and used as a nano-reactor to produce well-defined polymer nano-cylinders. Confirmed by small-angle X-ray scattering (SAXS), Raman and NMR spectrometry, monodispersed cylindrical micelles that contain a hydrophilic cavity with a diameter of 2.09 nm and a length of 4.26 nm were produced via co-assembling POSS-AD with hydrophilic liquids, such as H 2 O and HEMA in hydrophobic solvents. Taking the HEMA/POSS-AD cylindrical micelles as nano-reactors, polymerization of HEMA within the micelles results in polymer nano-cylinders (POSS-ADNPs) with a diameter of 2.24 nm and a length of 5.02 nm. The study confirmed that despite the inability to maintain specific shape in solution, low generation dendrimers form well-defined nano-containers or nano-reactors, which relies on co-assembling with hydrophilic guest molecules. These nano-reactors are robust enough to maintain their shape during the polymerization of the guest molecules. Polymer nano-cylinders with dimensions less than 10 nm can thus be produced from the HEMA/POSS-AD micelles. Since the chemical structure of low-generation dendrimers and the contents of the co-assembled nano-reactors can be easily adjusted, the concept holds the potential for the further developments of low-generation amphiphilic dendrimers.

  1. Nanoparticles Embedded in Amphiphilic Membranes for Carbon Dioxide Separation and Dehumidification.

    Science.gov (United States)

    Yong, Wai Fen; Ho, Yan Xun; Chung, Tai-Shung

    2017-10-23

    Polymers containing ethylene oxide (EO) groups have gained significant interest as the EO groups have favorable interactions with polar molecules such as H 2 O, quadrupolar molecules such as CO 2 , and metal ions. However, the main challenges of poly(ethylene oxide) (PEO) membranes are their weak mechanical properties and high crystallinity nature. The amphiphilic copolymer made from PEO terephthalate and poly(butylene terephthalate) (PEOT/PBT) comprises both hydrophilic and hydrophobic segments. The hydrophilic PEOT segment is thermosensitive, which facilities gas transports whereas the hydrophobic PBT segment is rigid, which provides mechanical robustness. This work demonstrates a new strategy to design amphiphilic mixed matrix membranes (MMMs) by incorporating zeolitic imidazolate framework, ZIF-71, into the PEOT/PBT copolymer. The resultant membrane shows an enhanced CO 2 permeability with an ideal CO 2 /N 2 selectivity surpassing the original PEOT/PBT and Robeson's Upper bound line. The nanoparticles-embedded amphiphilic membranes exhibit characteristics of high transparency and mechanical robustness. Mechanically strong composite hollow fiber membranes consisting of PEOT/PBT/ZIF-71 as the selective layer were also prepared. The resultant hollow fibers possess an excellent CO 2 permeance of 131 GPU (gas permeation units), CO 2 /N 2 selectivity of 52.6, H 2 O permeance of 9300 GPU and H 2 O/N 2 selectivity of 3700, showing great potential for industrial CO 2 capture and dehumidification. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. The effect of amphiphilic siloxane oligomers on fibroblast and keratinocyte proliferation and apoptosis.

    Science.gov (United States)

    Lynam, Emily C; Xie, Yan; Loli, Bree; Dargaville, Tim R; Leavesley, David I; George, Graeme A; Upton, Zee

    2010-11-01

    The formation of hypertrophic scars (HSF) is a frequent medical outcome of wound repair and often requires further therapy with treatments such as silicone gel sheets (SGS) or apoptosis-inducing agents, including bleomycin. Although widely used, knowledge regarding SGS and their mode of action is limited. Preliminary research has shown that small amounts of amphiphilic silicone present in SGS have the ability to move into skin during treatment. We demonstrate herein that a commercially available analogue of these amphiphilic siloxane species, the rake copolymer GP226, decreases collagen synthesis on exposure to cultures of fibroblasts derived from HSF. By size exclusion chromatography, GP226 was found to be a mixture of siloxane species, containing five fractions of different molecular weight. By studies of collagen production, cell viability and proliferation, it was revealed that a low molecular weight fraction (fraction IV) was the most active, reducing the number of viable cells present after treatment and thereby reducing collagen production as a result. On exposure of fraction IV to human keratinocytes, viability and proliferation were also significantly affected. HSF undergoing apoptosis after application of fraction IV were also detected via real-time microscopy and by using the TUNEL assay. Taken together, these data suggests that these amphiphilic siloxanes could be potential non-invasive substitutes to apoptotic-inducing chemical agents that are currently used as scar treatments.

  3. A calorimetric evaluation of the interaction of amphiphilic prodrugs of idebenone with a biomembrane model.

    Science.gov (United States)

    Pignatello, R; Intravaia, V D; Puglisi, G

    2006-07-15

    Lipoamino acids (LAA) are useful promoieties to modify physicochemical properties of drugs, namely lipophilicity and amphiphilicity. The resulting membrane-like character of drug-LAA conjugates can increase the absorption profile of drugs through cell membranes and biological barriers. To show the role of amphiphilicity with respect to lipophilicity in the interaction of drugs with biomembranes, in the present study we evaluated the mode of such an interaction of lipophilic conjugates of LAA with the antioxidant drug idebenone (IDE). DSC analysis and transfer kinetic studies were carried out using dimyristoylphosphatidylcholine (DMPC) multilamellar liposomes (MLVs) as a model. For comparison, two esters of IDE with alkanoic acids were synthesized and included in the analysis. The experimental results indicate that based on their different structure, IDE-LAA conjugates interacted at different levels with respect to pure IDE with DMPC bilayers. In particular, a progressive penetration inside the vesicles was observed upon incubation of IDE-LAA compounds with empty liposomes. The enhanced amphiphilicity of the drug due to the LAA moieties caused more complex interactions with DMPC bilayers, compared to those registered with the native drug or IDE alkanoate esters.

  4. Shape Recovery with Concomitant Mechanical Strengthening of Amphiphilic Shape Memory Polymers in Warm Water

    International Nuclear Information System (INIS)

    Zhang, Ben; DeBartolo, Janae E.; Song, Jie

    2017-01-01

    Maintaining adequate or enhancing mechanical properties of shape memory polymers (SMPs) after shape recovery in an aqueous environment are greatly desired for biomedical applications of SMPs as self-fitting tissue scaffolds or minimally invasive surgical implants. Here we report stable temporary shape fixing and facile shape recovery of biodegradable triblock amphiphilic SMPs containing a poly(ethylene glycol) (PEG) center block and flanking poly(lactic acid) or poly(lactic-co-glycolic acid) blocks in warm water, accompanied with concomitant enhanced mechanical strengths. Differential scanning calorimetry (DSC), wide-angle X-ray diffraction (WXRD) and small-angle X-ray scattering (SAXS) analyses revealed that the unique stiffening of the amphiphilic SMPs upon hydration was due to hydration-driven microphase separation and PEG crystallization. We further demonstrated that the chemical composition of degradable blocks in these SMPs could be tailored to affect the persistence of hydration-induced stiffening upon subsequent dehydration. These properties combined open new horizons for these amphiphilic SMPs for smart weight-bearing in vivo applications (e.g. as self-fitting intervertebral discs). In conclusion, this study also provides a new material design strategy to strengthen polymers in aqueous environment in general.

  5. Self-Assembly of Discrete Metal Complexes in Aqueous Solution via Block Copolypeptide Amphiphiles

    Directory of Open Access Journals (Sweden)

    Timothy J. Deming

    2013-01-01

    Full Text Available The integration of discrete metal complexes has been attracting significant interest due to the potential of these materials for soft metal-metal interactions and supramolecular assembly. Additionally, block copolypeptide amphiphiles have been investigated concerning their capacity for self-assembly into structures such as nanoparticles, nanosheets and nanofibers. In this study, we combined these two concepts by investigating the self-assembly of discrete metal complexes in aqueous solution using block copolypeptides. Normally, discrete metal complexes such as [Au(CN2]−, when molecularly dispersed in water, cannot interact with one another. Our results demonstrated, however, that the addition of block copolypeptide amphiphiles such as K183L19 to [Au(CN2]− solutions induced one-dimensional integration of the discrete metal complex, resulting in photoluminescence originating from multinuclear complexes with metal-metal interactions. Transmission electron microscopy (TEM showed a fibrous nanostructure with lengths and widths of approximately 100 and 20 nm, respectively, which grew to form advanced nanoarchitectures, including those resembling the weave patterns of Waraji (traditional Japanese straw sandals. This concept of combining block copolypeptide amphiphiles with discrete coordination compounds allows the design of flexible and functional supramolecular coordination systems in water.

  6. Synthesis and characterization of amorphous mesoporous silica using TEMPO-functionalized amphiphilic templates

    Energy Technology Data Exchange (ETDEWEB)

    Vries, Wilke de [Institute of Organic Chemistry, Westfälische Wilhelms-Universität Münster, Corrensstrasse 40, 48149 Münster (Germany); Doerenkamp, Carsten; Zeng, Zhaoyang [Institut für Physikalische Chemie, Westfälische Wilhelms-Universität Münster, Corrensstrasse 28/30, 48149 Münster (Germany); Oliveira, Marcos de [Instituto de Física em Sao Paulo, Universidade de Sao Paulo, Av. Trabalhador Saocarlense 400, Sao Carlos, S.P. 13560 590 (Brazil); Niehaus, Oliver; Pöttgen, Rainer [Institut für Anorganische und Analytische Chemie, Westfälische Wilhelms-Universität Münster, Corrensstrasse 28/30, 48149 Münster (Germany); Studer, Armido, E-mail: studer@uni-muenster.de [Institute of Organic Chemistry, Westfälische Wilhelms-Universität Münster, Corrensstrasse 40, 48149 Münster (Germany); Eckert, Hellmut, E-mail: eckerth@uni-muenster.de [Institut für Physikalische Chemie, Westfälische Wilhelms-Universität Münster, Corrensstrasse 28/30, 48149 Münster (Germany); Instituto de Física em Sao Paulo, Universidade de Sao Paulo, Av. Trabalhador Saocarlense 400, Sao Carlos, S.P. 13560 590 (Brazil)

    2016-05-15

    Inorganic–organic hybrid materials based on amorphous mesoporous silica containing organized nitroxide radicals within its mesopores have been prepared using the micellar self-assembly of TEOS solutions containing the nitroxide functionalized amphiphile (4-(N,N-dimethyl-N-hexadecylammonium)-2,2,6, 6-tetramethyl-piperidin-N-oxyl-iodide) (CAT-16). This template has been used both in its pure form and in various mixtures with cetyl trimethylammonium bromide (CTAB). The samples have been characterized by chemical analysis, N{sub 2} sorption studies, magnetic susceptibility measurements, and various spectroscopic methods. While electron paramagnetic resonance (EPR) spectra indicate that the strength of the intermolecular spin–spin interactions can be controlled via the CAT-16/CTAB ratio, nuclear magnetic resonance (NMR) data suggest that these interactions are too weak to facilitate cooperative magnetism. - Graphical abstract: The amphiphilic radical CAT-16 is used as a template for the synthesis of amorphous mesoporous silica. The resulting paramagnetic hybrid materials are characterized by BET, FTIR, NMR, EPR and magnetic susceptibility studies. - Highlights: • Amphiphilic CAT-16 as a template for mesoporous silica. • Comprehensive structural characterization by BET, FTIR; EPR and NMR. • Strength of radical-radical interactions tuable within CAT-16/CTAB mixtures.

  7. Design and application of cationic amphiphilic β-cyclodextrin derivatives as gene delivery vectors

    Science.gov (United States)

    Wan, Ning; Huan, Meng-Lei; Ma, Xi-Xi; Jing, Zi-Wei; Zhang, Ya-Xuan; Li, Chen; Zhou, Si-Yuan; Zhang, Bang-Le

    2017-11-01

    The nano self-assembly profiles of amphiphilic gene delivery vectors could improve the density of local cationic head groups to promote their DNA condensation capability and enhance the interaction between cell membrane and hydrophobic tails, thus increasing cellular uptake and gene transfection. In this paper, two series of cationic amphiphilic β-cyclodextrin (β-CD) derivatives were designed and synthesized by using 6-mono-OTs-β-CD (1) as the precursor to construct amphiphilic gene vectors with different building blocks in a selective and controlled manner. The effect of different type and degree of cationic head groups on transfection and the endocytic mechanism of β-CD derivatives/DNA nanocomplexes were also investigated. The results demonstrated that the designed β-cyclodextrin derivatives were able to compact DNA to form stable nanocomplexes and exhibited low cytotoxicity. Among them, PEI-1 with PEI head group showed enhanced transfection activity, significantly higher than commercially available agent PEI25000 especially in the presence of serum, showing potential application prospects in clinical trials. Moreover, the endocytic uptake mechanism involved in the gene transfection of PEI-1 was mainly through caveolae-mediated endocytosis, which could avoid the lysosomal degradation of loaded gene, and had great importance for improving gene transfection activity.

  8. Biopharmaceuticals: From peptide to drug

    Science.gov (United States)

    Hannappel, Margarete

    2017-08-01

    Biologics are therapeutic proteins or peptides that are produced by means of biological processes within living organisms and cells. They are highly specific molecules and play a crucial role as therapeutics for the treatment of severe and chronic diseases (e.g. cancer, rheumatoid arthritis, diabetes, autoimmune disorders). The development of new biologics and biologics-based drugs gains more and more importance in the fight against various diseases. A short overview on biotherapeutical drug development is given. Cone snails are a large group of poisonous, predatory sea snails with more than 700 species. They use a very powerful venom which rapidly inactivates and paralyzes their prey. Most bioactive venom components are small peptides (conotoxins, conopeptides) which are precisely directed towards a specific target (e.g. ion channel, receptors). Due to their small size, their precision and speed of action, naturally occurring cone snail venom peptides represent an attractive source for the identification and design of novel biological drug entities. The Jagna cone snail project is an encouraging initiative to map the ecological variety of cone snails around the island of Bohol (Philippines) and to conserve the biological information for potential future application.

  9. Plant peptide hormone signalling.

    Science.gov (United States)

    Motomitsu, Ayane; Sawa, Shinichiro; Ishida, Takashi

    2015-01-01

    The ligand-receptor-based cell-to-cell communication system is one of the most important molecular bases for the establishment of complex multicellular organisms. Plants have evolved highly complex intercellular communication systems. Historical studies have identified several molecules, designated phytohormones, that function in these processes. Recent advances in molecular biological analyses have identified phytohormone receptors and signalling mediators, and have led to the discovery of numerous peptide-based signalling molecules. Subsequent analyses have revealed the involvement in and contribution of these peptides to multiple aspects of the plant life cycle, including development and environmental responses, similar to the functions of canonical phytohormones. On the basis of this knowledge, the view that these peptide hormones are pivotal regulators in plants is becoming increasingly accepted. Peptide hormones are transcribed from the genome and translated into peptides. However, these peptides generally undergo further post-translational modifications to enable them to exert their function. Peptide hormones are expressed in and secreted from specific cells or tissues. Apoplastic peptides are perceived by specialized receptors that are located at the surface of target cells. Peptide hormone-receptor complexes activate intracellular signalling through downstream molecules, including kinases and transcription factors, which then trigger cellular events. In this chapter we provide a comprehensive summary of the biological functions of peptide hormones, focusing on how they mature and the ways in which they modulate plant functions. © 2015 Authors; published by Portland Press Limited.

  10. Comprehensive computational design of ordered peptide macrocycles

    Energy Technology Data Exchange (ETDEWEB)

    Hosseinzadeh, Parisa; Bhardwaj, Gaurav; Mulligan, Vikram K.; Shortridge, Matthew D.; Craven, Timothy W.; Pardo-Avila, Fatima; Rettie, Stephan A.; Kim, David E.; Silva, Daniel A.; Ibrahim, Yehia M.; Webb, Ian K.; Cort, John R.; Adkins, Joshua N.; Varani, Gabriele; Baker, David

    2017-12-14

    Mixed chirality peptide macrocycles such as cyclosporine are among the most potent therapeutics identified to-date, but there is currently no way to systematically search through the structural space spanned by such compounds for new drug candidates. Natural proteins do not provide a useful guide: peptide macrocycles lack regular secondary structures and hydrophobic cores and have different backbone torsional constraints. Hence the development of new peptide macrocycles has been approached by modifying natural products or using library selection methods; the former is limited by the small number of known structures, and the latter by the limited size and diversity accessible through library-based methods. To overcome these limitations, here we enumerate the stable structures that can be adopted by macrocyclic peptides composed of L and D amino acids. We identify more than 200 designs predicted to fold into single stable structures, many times more than the number of currently available unbound peptide macrocycle structures. We synthesize and characterize by NMR twelve 7-10 residue macrocycles, 9 of which have structures very close to the design models in solution. NMR structures of three 11-14 residue bicyclic designs are also very close to the computational models. Our results provide a nearly complete coverage of the rich space of structures possible for short peptide based macrocycles unparalleled for other molecular systems, and vastly increase the available starting scaffolds for both rational drug design and library selection methods.

  11. SPdb – a signal peptide database

    Directory of Open Access Journals (Sweden)

    Tan Tin

    2005-10-01

    Full Text Available Abstract Background The signal peptide plays an important role in protein targeting and protein translocation in both prokaryotic and eukaryotic cells. This transient, short peptide sequence functions like a postal address on an envelope by targeting proteins for secretion or for transfer to specific organelles for further processing. Understanding how signal peptides function is crucial in predicting where proteins are translocated. To support this understanding, we present SPdb signal peptide database http://proline.bic.nus.edu.sg/spdb, a repository of experimentally determined and computationally predicted signal peptides. Results SPdb integrates information from two sources (a Swiss-Prot protein sequence database which is now part of UniProt and (b EMBL nucleotide sequence database. The database update is semi-automated with human checking and verification of the data to ensure the correctness of the data stored. The latest release SPdb release 3.2 contains 18,146 entries of which 2,584 entries are experimentally verified signal sequences; the remaining 15,562 entries are either signal sequences that fail to meet our filtering criteria or entries that contain unverified signal sequences. Conclusion SPdb is a manually curated database constructed to support the understanding and analysis of signal peptides. SPdb tracks the major updates of the two underlying primary databases thereby ensuring that its information remains up-to-date.

  12. Characterization of the Cu(Π) and Zn(Π) binding to the Amyloid-β short peptides by both the Extended X-ray Absorption Fine Structure and the Synchrotron Radiation Circular Dichroism spectroscopy

    Science.gov (United States)

    Zhang, Zhiyin; Sun, Shuaishuai; Xu, Jianhua; Zhang, Jing; Huang, Yan; Zhang, Bingbing; Tao, Ye

    2013-04-01

    Alzheimer's disease (AD) is a progressive and devastating neurodegenerative pathology, clinically characterized by dementia, cognitive impairment, personality disorders and memory loss. It is generally accepted that, misfolding of Aβ peptides is the key element in pathogenesis and the secondary structure of Aβ can be changed to major β-strand with reasons unknown yet. Many studies have shown that the misfolding may be linked with some biometals, mainly copper and zinc ions. To characterize interactions of Aβ and metal ions, we utilized both the extended X-ray fine structure spectroscopy (EXAFS) and the synchrotron radiation circular dichroism spectroscopy (SRCD). Aβ (13-22), Aβ (13-21), Aβ (E22G) and Aβ(HH-AA) were selected to study the mechanism of copper and zinc binding to Aβ. We found that Cu interaction with H13 and H14 residues led to the disappearance of the PPΠ, while the Cu binding E22 residue caused a remarkable conformation change to β-sheet enrichment. The Zn ion, in contrast, made little effect on the conformation and it coordinated to only one histidine (H residue) or not.

  13. Antimicrobial Peptides in Reptiles

    Science.gov (United States)

    van Hoek, Monique L.

    2014-01-01

    Reptiles are among the oldest known amniotes and are highly diverse in their morphology and ecological niches. These animals have an evolutionarily ancient innate-immune system that is of great interest to scientists trying to identify new and useful antimicrobial peptides. Significant work in the last decade in the fields of biochemistry, proteomics and genomics has begun to reveal the complexity of reptilian antimicrobial peptides. Here, the current knowledge about antimicrobial peptides in reptiles is reviewed, with specific examples in each of the four orders: Testudines (turtles and tortosises), Sphenodontia (tuataras), Squamata (snakes and lizards), and Crocodilia (crocodilans). Examples are presented of the major classes of antimicrobial peptides expressed by reptiles including defensins, cathelicidins, liver-expressed peptides (hepcidin and LEAP-2), lysozyme, crotamine, and others. Some of these peptides have been identified and tested for their antibacterial or antiviral activity; others are only predicted as possible genes from genomic sequencing. Bioinformatic analysis of the reptile genomes is presented, revealing many predicted candidate antimicrobial peptides genes across this diverse class. The study of how these ancient creatures use antimicrobial peptides within their innate immune systems may reveal new understandings of our mammalian innate immune system and may also provide new and powerful antimicrobial peptides as scaffolds for potential therapeutic development. PMID:24918867

  14. Opposing effects of cationic antimicrobial peptides and divalent cations on bacterial lipopolysaccharides

    Science.gov (United States)

    Smart, Matthew; Rajagopal, Aruna; Liu, Wing-Ki; Ha, Bae-Yeun

    2017-10-01

    The permeability of the bacterial outer membrane, enclosing Gram-negative bacteria, depends on the interactions of the outer, lipopolysaccharide (LPS) layer, with surrounding ions and molecules. We present a coarse-grained model for describing how cationic amphiphilic molecules (e.g., antimicrobial peptides) interact with and perturb the LPS layer in a biologically relevant medium, containing monovalent and divalent salt ions (e.g., Mg2+). In our approach, peptide binding is driven by electrostatic and hydrophobic interactions and is assumed to expand the LPS layer, eventually priming it for disruption. Our results suggest that in parameter ranges of biological relevance (e.g., at micromolar concentrations) the antimicrobial peptide magainin 2 effectively disrupts the LPS layer, even though it has to compete with Mg2+ for the layer. They also show how the integrity of LPS is restored with an increasing concentration of Mg2+. Using the approach, we make a number of predictions relevant for optimizing peptide parameters against Gram-negative bacteria and for understanding bacterial strategies to develop resistance against cationic peptides.

  15. Measurement of troponin and natriuretic peptides shortly after admission in patients with heart failure-does it add useful prognostic information? An analysis of the Value of Endothelin Receptor Inhibition with Tezosentan in Acute heart failure Studies (VERITAS).

    Science.gov (United States)

    Cleland, John G F; Teerlink, John R; Davison, Beth A; Shoaib, Ahmad; Metra, Marco; Senger, Stefanie; Milo, Olga; Cotter, Gad; Bourge, Robert C; Parker, John D; Jondeau, Guillaume; Krum, Henry; O'Connor, Christopher M; Torre-Amione, Guillermo; van Veldhuisen, Dirk J; McMurray, John J V

    2017-06-01

    Plasma concentrations of B-type natriuretic peptide (BNP) and troponin are often measured for diagnostic purposes when patients are admitted with heart failure, but their prognostic value when measured soon after admission is uncertain. We aimed to investigate the added prognostic value of admission measurements of BNP and troponins in patients with acute heart failure. Multivariable prognostic models for death or any worsening heart failure (WHF) or rehospitalization for WHF by 30 days, 30-day death or rehospitalization for WHF, and 90-day mortality were constructed using baseline data from the Value of Endothelin Receptor Inhibition with Tezosentan in Acute heart failure Studies (VERITAS) including BNP and troponin I. Of 1347 patients, the median (interquartile range) value of BNP was 422 (156-945) pg/mL and 855 (63%) had measurable troponin I. By 30 days, 432 patients had died or experienced WHF. Clinical variables had only moderate predictive performance that was not substantially improved by BNP or troponin I (c-indices 0.6528 and 0.6595, respectively). By 30 days, 150 patients died or were rehospitalized for WHF. The c-index using clinical variables (0.6855) was not improved by adding biomarkers. By 90 days, 135 patients had died. The c-index for mortality was somewhat better than for composite outcomes (0.7394) but improved little with biomarkers (0.7461). Routine clinical data recorded at the time of admission in patients with acute heart failure are poor at predicting recurrent admissions but somewhat better at predicting mortality. Neither BNP nor troponin measured at admission improved predictions; measurement closer to discharge, or of other novel biomarkers, might perform differently. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

  16. Differential Interaction of Antimicrobial Peptides with Lipid Structures Studied by Coarse-Grained Molecular Dynamics Simulations

    Directory of Open Access Journals (Sweden)

    Galo E. Balatti

    2017-10-01

    Full Text Available In this work; we investigated the differential interaction of amphiphilic antimicrobial peptides with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC lipid structures by means of extensive molecular dynamics simulations. By using a coarse-grained (CG model within the MARTINI force field; we simulated the peptide–lipid system from three different initial configurations: (a peptides in water in the presence of a pre-equilibrated lipid bilayer; (b peptides inside the hydrophobic core of the membrane; and (c random configurations that allow self-assembled molecular structures. This last approach allowed us to sample the structural space of the systems and consider cooperative effects. The peptides used in our simulations are aurein 1.2 and maculatin 1.1; two well-known antimicrobial peptides from the Australian tree frogs; and molecules that present different membrane-perturbing behaviors. Our results showed differential behaviors for each type of peptide seen in a different organization that could guide a molecular interpretation of the experimental data. While both peptides are capable of forming membrane aggregates; the aurein 1.2 ones have a pore-like structure and exhibit a higher level of organization than those conformed by maculatin 1.1. Furthermore; maculatin 1.1 has a strong tendency to form clusters and induce curvature at low peptide–lipid ratios. The exploration of the possible lipid–peptide structures; as the one carried out here; could be a good tool for recognizing specific configurations that should be further studied with more sophisticated methodologies.

  17. Peptide catalysed prebiotic polymerization of RNA

    DEFF Research Database (Denmark)

    Wieczorek, Rafal; Luisi, Pier Luigi; Monnard, Pierre-Alain

    A short peptide composed of only two amino acid residues, serine and histidine, is here reported to enable oligomerization of RNA monomers. SerHis dipeptide was previously reported to catalyse formation of peptide bonds (Gorlero et al. 2009) as well as possessing broad hydrolytic activities...... – in such environment hydrolysis is thermodynamically favoured over condensation. However, the thermodynamic equilibrium towards condensation can be shifted even in this environment. In this poster we describe a prebiotically plausible system in which the SerHis dipeptide acts as catalyst for the formation of RNA...... these conditions, most of the water is in the form of ice crystals and the other reactants are upconcentrated in the remaining liquid micro-inclusions, hence creating an environment with low water activity in which condensation reactions can occur. The ability of simple peptides to catalyse RNA synthesis could...

  18. Viral O-GalNAc peptide epitopes

    DEFF Research Database (Denmark)

    Olofsson, Sigvard; Blixt, Klas Ola; Bergström, Tomas

    2016-01-01

    meningitis patients, CSF antibodies are focussed to only one single glycoform peptide of a major viral glycoprotein. Thus, dependent on the viral disease, the serological response may be variable or constant with respect to the number of targeted peptide glycoforms. Mapping of these epitopes relies......Viral envelope glycoproteins are major targets for antibodies that bind to and inactivate viral particles. The capacity of a viral vaccine to induce virus-neutralizing antibodies is often used as a marker for vaccine efficacy. Yet the number of known neutralization target epitopes is restricted...... owing to various viral escape mechanisms. We expand the range of possible viral glycoprotein targets, by presenting a previously unknown type of viral glycoprotein epitope based on a short peptide stretch modified with small O-linked glycans. Besides being immunologically active, these epitopes have...

  19. Insulin C-peptide test

    Science.gov (United States)

    C-peptide ... the test depends on the reason for the C-peptide measurement. Ask your health care provider if ... C-peptide is measured to tell the difference between insulin the body produces and insulin someone injects ...

  20. Dimensional Control and Morphological Transformations of Supramolecular Polymeric Nanofibers Based on Cofacially-Stacked Planar Amphiphilic Platinum(II) Complexes.

    Science.gov (United States)

    Robinson, Matthew E; Nazemi, Ali; Lunn, David J; Hayward, Dominic W; Boott, Charlotte E; Hsiao, Ming-Siao; Harniman, Robert L; Davis, Sean A; Whittell, George R; Richardson, Robert M; De Cola, Luisa; Manners, Ian

    2017-09-26

    Square-planar platinum(II) complexes often stack cofacially to yield supramolecular fiber-like structures with interesting photophysical properties. However, control over fiber dimensions and the resulting colloidal stability is limited. We report the self-assembly of amphiphilic Pt(II) complexes with solubilizing ancillary ligands based on polyethylene glycol [PEG n , where n = 16, 12, 7]. The complex with the longest solubilizing PEG ligand, Pt-PEG 16 , self-assembled to form polydisperse one-dimensional (1D) nanofibers (diameters fibers of length up to ca. 400 nm. The fiber lengths were dependent on the Pt-PEG 16 complex to seed mass ratio in a manner analogous to a living covalent polymerization of molecular monomers. Moreover, the fiber lengths were unchanged in solution after 1 week and were therefore "static" with respect to interfiber exchange processes on this time scale. In contrast, similarly formed near-uniform fibers of Pt-PEG 12 exhibited dynamic behavior that led to broadening of the length distribution within 48 h. After aging for 4 weeks in solution, Pt-PEG 12 fibers partially evolved into 2D platelets. Furthermore, self-assembly of Pt-PEG 7 yielded only transient fibers which rapidly evolved into 2D platelets. On addition of further fiber-forming Pt complex (Pt-PEG 16 ), the platelets formed assemblies via the growth of fibers selectively from their short edges. Our studies demonstrate that when interfiber dynamic exchange is suppressed, dimensional control and hierarchical structure formation are possible for supramolecular polymers through the use of kinetically controlled seeded growth methods.

  1. Core–Shell Structure and Aggregation Number of Micelles Composed of Amphiphilic Block Copolymers and Amphiphilic Heterografted Polymer Brushes Determined by Small-Angle X-ray Scattering

    Energy Technology Data Exchange (ETDEWEB)

    Szymusiak, Magdalena; Kalkowski, Joseph; Luo, Hanying; Donovan, Alexander J.; Zhang, Pin; Liu, Chang; Shang, Weifeng; Irving, Thomas; Herrera-Alonso, Margarita; Liu, Ying (JHU); (IIT); (UIC)

    2017-08-31

    A large group of functional nanomaterials employed in biomedical applications, including targeted drug delivery, relies on amphiphilic polymers to encapsulate therapeutic payloads via self-assembly processes. Knowledge of the micelle structures will provide critical insights into design of polymeric drug delivery systems. Core–shell micelles composed of linear diblock copolymers poly(ethylene glycol)-b-poly(caprolactone) (PEG-b-PCL), poly(ethylene oxide)-b-poly(lactic acid) (PEG-b-PLA), as well as a heterografted brush consisting of a poly(glycidyl methacrylate) backbone with PEG and PLA branches (PGMA-g-PEG/PLA) were characterized by dynamic light scattering (DLS) and small-angle X-ray scattering (SAXS) measurements to gain structural information regarding the particle morphology, core–shell size, and aggregation number. The structural information at this quasi-equilibrium state can also be used as a reference when studying the kinetics of polymer micellization.

  2. Core–Shell Structure and Aggregation Number of Micelles Composed of Amphiphilic Block Copolymers and Amphiphilic Heterografted Polymer Brushes Determined by Small-Angle X-ray Scattering

    Energy Technology Data Exchange (ETDEWEB)

    Szymusiak, Magdalena [Department; Kalkowski, Joseph [Department; Luo, Hanying [Department; Donovan, Alexander J. [Department; Zhang, Pin [Department; Liu, Chang [Department; Shang, Weifeng [Department; Irving, Thomas [Department; Herrera-Alonso, Margarita [Department; Liu, Ying [Department; Department

    2017-08-16

    A large group of functional nanomaterials employed in biomedical applications, including targeted drug delivery, relies on amphiphilic polymers to encapsulate therapeutic payloads via self-assembly processes. Knowledge of the micelle structures will provide critical insights into design of polymeric drug delivery systems. Core–shell micelles composed of linear diblock copolymers poly(ethylene glycol)-b-poly(caprolactone) (PEG-b-PCL), poly(ethylene oxide)-b-poly(lactic acid) (PEG-b-PLA), as well as a heterografted brush consisting of a poly(glycidyl methacrylate) backbone with PEG and PLA branches (PGMA-g-PEG/PLA) were characterized by dynamic light scattering (DLS) and small-angle X-ray scattering (SAXS) measurements to gain structural information regarding the particle morphology, core–shell size, and aggregation number. The structural information at this quasi-equilibrium state can also be used as a reference when studying the kinetics of polymer micellization.

  3. LL-37-derived short antimicrobial peptide KR-12-a5 and its d-amino acid substituted analogs with cell selectivity, anti-biofilm activity, synergistic effect with conventional antibiotics, and anti-inflammatory activity.

    Science.gov (United States)

    Kim, Eun Young; Rajasekaran, Ganesan; Shin, Song Yub

    2017-08-18

    KR-12-a5 is a 12-meric α-helical antimicrobial peptide (AMP) with dual antimicrobial and anti-inflammatory activities designed from human cathelicidin LL-37. We designed and synthesized a series of d-amino acid-substituted analogs of KR-12-a5 with the aim of developing novel α-helical AMPs that possess higher cell selectivity than KR-12-a5, while maintaining the anti-inflammatory activity. d-amino acid incorporation into KR-12-a5 induced a significant improvement in the cell selectivity by 2.6- to 13.6-fold as compared to KR-12-a5, while maintaining the anti-inflammatory activity. Among the three analogs, KR-12-a5 (6- D L) with d-amino acid in the polar-nonpolar interface (Leu 6 ) showed the highest cell selectivity (therapeutic index: 61.2). Similar to LL-37, KR-12-a5 and its analogs significantly inhibited the expression and secretion of NO, TNF-α, IL-6 and MCP-1 from LPS-stimulated RAW264.7 cells. KR-12-a5 and its analogs showed a more potent antimicrobial activity against antibiotic-resistant bacteria, including clinically isolated MRSA, MDRPA, and VREF than LL-37 and melittin. Furthermore, compared to LL-37, KR-12-a5 and its analogs showed greater synergistic effects with conventional antibiotics, such as chloramphenicol, ciprofloxacin, and oxacillin against MDRPA; KR-12-a5 and its analogs had a FICI range between 0.25 and 0.5, and LL-37 had a range between 0.75 and 1.5. KR-12-a5 and its analogs were found to be more effective anti-biofilm agents against MDRPA than LL-37. In addition, KR-12-a5 and its analogs maintained antimicrobial activity in physiological salts and human serum. SYTOX Green uptake and membrane depolarization studies revealed that KR-12-a5 and its analogs kills microbial cells by permeabilizing the cell membrane and damaging membrane integrity. Taken together, our results suggest that KR-12-a5 and its analogs can be developed further as novel antimicrobial/anti-inflammatory agents to treat antibiotic-resistant infections. Copyright

  4. Cationic Antimicrobial Peptides Inactivate Shiga Toxin-Encoding Bacteriophages

    Directory of Open Access Journals (Sweden)

    Manuel E. Del Cogliano

    2017-12-01

    Full Text Available Shiga toxin (Stx is the principal virulence factor during Shiga toxin-producing Escherichia coli (STEC infections. We have previously reported the inactivation of bacteriophage encoding Stx after treatment with chitosan, a linear polysaccharide polymer with cationic properties. Cationic antimicrobial peptides (cAMPs are short linear aminoacidic sequences, with a positive net charge, which display bactericidal or bacteriostatic activity against a wide range of bacterial species. They are promising novel antibiotics since they have shown bactericidal effects against multiresistant bacteria. To evaluate whether cationic properties are responsible for bacteriophage inactivation, we tested seven cationic peptides with proven antimicrobial activity as anti-bacteriophage agents, and one random sequence cationic peptide with no antimicrobial activity as a control. We observed bacteriophage inactivation after incubation with five cAMPs, but no inactivating activity was observed with the random sequence cationic peptide or with the non-alpha helical cAMP Omiganan. Finally, to confirm peptide-bacteriophage interaction, zeta potential was analyzed by following changes on bacteriophage surface charges after peptide incubation. According to our results we could propose that: (1 direct interaction of peptides with phage is a necessary step for bacteriophage inactivation, (2 cationic properties are necessary but not sufficient for bacteriophage inactivation, and (3 inactivation by cationic peptides could be sequence (or structure specific. Overall our data suggest that these peptides could be considered a new family of molecules potentially useful to decrease bacteriophage replication and Stx expression.

  5. Characterization of beta-turn and Asx-turns mimicry in a model peptide: stabilization via C--H . . . O interaction.

    Science.gov (United States)

    Thakur, A K; Kishore, R

    2006-04-15

    The chemical synthesis and single-crystal X-ray diffraction analysis of a model peptide, Boc-Thr-Thr-NH2 (1) comprised of proteinogenic residues bearing an amphiphilic Cbeta -stereogenic center, has been described. Interestingly, the analysis of its molecular structure revealed the existence of a distinct conformation that mimics a typical beta-turn and Asx-turns, i.e., the two Thr residues occupy the left- and right-corner positions. The main-chain torsion angles of the N- and C-terminal residues i.e., semiextended: phi = -68.9 degrees , psi = 128.6 degrees ; semifolded: phi = -138.1 degrees , psi = 2.5 degrees conformations, respectively, in conjunction with a gauche- disposition of the obligatory C-terminus Thr CgammaH3 group, characterize the occurrence of the newly described beta-turn- and Asx-turns-like topology. The preferred molecular structure is suggested to be stabilized by an effective nonconventional main-chain to side-chain Ci=O . . . H--Cgamma(i+2)-type intraturn hydrogen bond. Noteworthy, the observed topology of the resulting 10-membered hydrogen-bonded ring is essentially similar to the one perceived for a classical beta-turn and the Asx-turns, stabilized by a conventional intraturn hydrogen bond. Considering the signs as well as magnitudes of the backbone torsion angles and the orientation of the central peptide bond, the overall mimicked topology resembles the type II beta-turn or type II Asx-turns. An analysis of Xaa-Thr sequences in high-resolution X-ray elucidated protein structures revealed the novel topology prevalence in functional proteins (unpublished). In view of indubitable structural as well as functional importance of nonconventional interactions in bioorganic and biomacromolecules, we intend to highlight the participation of Thr CgammaH in the creation of a short-range C=O . . . H--Cgamma -type interaction in peptides and proteins. Copyright 2006 Wiley Periodicals, Inc.

  6. Human Antimicrobial Peptides and Proteins

    Directory of Open Access Journals (Sweden)

    Guangshun Wang

    2014-05-01

    medicine to combat drug-resistant superbugs, fungi, viruses, parasites, or cancer. Alternatively, multiple factors (e.g., albumin, arginine, butyrate, calcium, cyclic AMP, isoleucine, short-chain fatty acids, UV B light, vitamin D, and zinc are able to induce the expression of antimicrobial peptides, opening new avenues to the development of anti-infectious drugs.

  7. Construction of amphiphilic segments on polypropylene nonwoven surface and its application in removal of endocrine disrupting compounds (EDCs) from aqueous solution

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Kai [State Key Laboratory of Hollow Fiber Membrane Materials and Processes, Tianjin Polytechnic University, Tianjin 300160 (China); School of Environmental and Chemical Engineering, Tianjin Polytechnic University, Tianjin 300160 (China); Wei, Junfu, E-mail: junfuwei1963@163.com [State Key Laboratory of Hollow Fiber Membrane Materials and Processes, Tianjin Polytechnic University, Tianjin 300160 (China); School of Environmental and Chemical Engineering, Tianjin Polytechnic University, Tianjin 300160 (China); Zhou, Xiangyu [State Key Laboratory of Hollow Fiber Membrane Materials and Processes, Tianjin Polytechnic University, Tianjin 300160 (China); School of Environmental and Chemical Engineering, Tianjin Polytechnic University, Tianjin 300160 (China); School of Materials Science and Engineering, Tianjin Polytechnic University, Tianjin 300160 (China); Liu, Nana [State Key Laboratory of Hollow Fiber Membrane Materials and Processes, Tianjin Polytechnic University, Tianjin 300160 (China); School of Environmental and Chemical Engineering, Tianjin Polytechnic University, Tianjin 300160 (China)

    2015-05-15

    Highlights: • The amphiphilic segments on polypropylene nonwoven surface were constructed successfully. • The adsorption behavior for EDCs of the amphiphilic adsorption materials was systematically studied. • The novel amphiphilic adsorption materials have broad application prospects in EDCs removal from aqueous solution. - Abstract: The amphiphilic segments on polypropylene nonwoven (PP nonwoven) surface were constructed using the ultraviolet (UV) irradiation graft polymerization for the removal of endocrine disrupting compounds (EDCs) with different polarity from aqueous solution. The stearyl acrylate (SA) as hydrophobic functional monomer was introduced onto the surface of PP nonwoven fabric at first stage and then the hydroxyethyl acrylate (HEA) as hydrophilic functional monomer was introduced subsequently. The effect of functional monomer concentration and UV irradiation time on grafting ratio was studied and discussed. The novel amphiphilic structure was designed and constructed based on adsorption capacity for the target micropollutants. The structure and composition of the amphiphilic adsorption materials were characterized by Fourier transform infrared spectrometer (FTIR), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM) and contact angle (CA). The adsorption behaviors for EDCs of the amphiphilic adsorption materials were studied and the results indicated that the adsorption capacity and adsorption rate were superior to single SA grafted PP nonwoven (PP-g-SA) and single HEA grafted PP nonwoven (PP-g-HEA). The novel amphiphilic adsorption material was efficient for the removal of EDCs with different polarity and could be utilized as a potential adsorption material for removing EDCs from aqueous solution.

  8. Construction of amphiphilic segments on polypropylene nonwoven surface and its application in removal of endocrine disrupting compounds (EDCs) from aqueous solution

    International Nuclear Information System (INIS)

    Liu, Kai; Wei, Junfu; Zhou, Xiangyu; Liu, Nana

    2015-01-01

    Highlights: • The amphiphilic segments on polypropylene nonwoven surface were constructed successfully. • The adsorption behavior for EDCs of the amphiphilic adsorption materials was systematically studied. • The novel amphiphilic adsorption materials have broad application prospects in EDCs removal from aqueous solution. - Abstract: The amphiphilic segments on polypropylene nonwoven (PP nonwoven) surface were constructed using the ultraviolet (UV) irradiation graft polymerization for the removal of endocrine disrupting compounds (EDCs) with different polarity from aqueous solution. The stearyl acrylate (SA) as hydrophobic functional monomer was introduced onto the surface of PP nonwoven fabric at first stage and then the hydroxyethyl acrylate (HEA) as hydrophilic functional monomer was introduced subsequently. The effect of functional monomer concentration and UV irradiation time on grafting ratio was studied and discussed. The novel amphiphilic structure was designed and constructed based on adsorption capacity for the target micropollutants. The structure and composition of the amphiphilic adsorption materials were characterized by Fourier transform infrared spectrometer (FTIR), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM) and contact angle (CA). The adsorption behaviors for EDCs of the amphiphilic adsorption materials were studied and the results indicated that the adsorption capacity and adsorption rate were superior to single SA grafted PP nonwoven (PP-g-SA) and single HEA grafted PP nonwoven (PP-g-HEA). The novel amphiphilic adsorption material was efficient for the removal of EDCs with different polarity and could be utilized as a potential adsorption material for removing EDCs from aqueous solution

  9. Effects of small ionic amphiphilic additives on reverse microemulsion morphology.

    Science.gov (United States)

    Hatzopoulos, Marios Hopkins; James, Craig; Rogers, Sarah; Grillo, Isabelle; Dowding, Peter J; Eastoe, Julian

    2014-05-01

    Initial studies (Hopkins Hatzopoulos et al. (2013)) have shown that ionic hydrotropic additives can drive a sphere-to-cylinder (ellipsoid) transition in water-in-oil (w/o) microemulsions stabilized by the anionic surfactant Aerosol-OT; however the origins of this behaviour remained unclear. Here systematic effects of chemical structure are explored with a new set of hydrotropes, in terms of an aromatic versus a saturated cyclic hydrophobic group, and linear chain length of alkyl carboxylates. It is proposed that hydrotrope-induced microemulsion sphere-to-cylinder (ellipsoid) transitions are linked to additive hydrophobicity, and so a correlation between the bulk aqueous phase critical aggregation concentration (cac) and perturbation of microemulsion structure is expected. Water-in-oil microemulsions were formulated as a function of water content w (= [water]/[AOT]) and concentration of different hydrotropes, being either cyclic (sodium benzoate or sodium cyclohexanoate), or linear chain systems (sodium hexanoate, sodium heptanoate and sodium octanoate). Phase behaviour studies were performed as a function of w, additive type and temperature at total surfactant concentration [ST]=0.10M and constant mole fraction x=0.10 (x=[hydrotrope]/[ST]). Microemulsion domain structures were investigated by small-angle neutron scattering (SANS), and these data were fitted by structural models to yield information on the shapes (spheres, ellipsoids or cylinders) and sizes of the nanodroplets. Under the conditions of study hydrotrope chemical structure has a significant effect on microemulsion structure: sodium cyclohexanoate does not induce the formation of cylindrical/ellipsoidal nanodroplets, whereas the aromatic analogue sodium benzoate does. Furthermore, the short chain sodium hexanoate does not cause anisotropic microemulsions, but the more hydrophobic longer chain heptanoate and octanoate analogues do induce sphere-to-ellipsoid transitions. This study shows that underlying

  10. Radionuclide therapy with peptides: bench to bedside

    International Nuclear Information System (INIS)

    Das, Tapas

    2016-01-01

    Peptides, which are short chains of amino acids linked by the peptide (amide) bond, play an important role in the management of various types of ailments. Recently, use of radiolabeled peptides has emerged as one of the prime treatment modality for combating against a variety of cancers. At present, 'Peptide Receptor Radionuclide Therapy' (PRRNT) employing 177 Lu-DOTA-TATE (lutetium-177 labeled DOTA coupled Tyr 3 -Octrotate) is considered as the only viable treatment modality for the patients suffering from inoperable and disseminated neuroendocrine cancers over expressing somatostatin receptors. In the last couple of years, clinical evaluations carried outwith 177 Lu-PSMA-617 (PSMA: Prostate Specific Membrane Antigen) have shown encouraging results in targeted radionuclide therapy of patients suffering from prostate cancer. These agents are available from a limited number of foreign suppliers; but are prohibitively expensive, which makes these agents almost unaffordable to most of the Indian patients. Therefore, it was necessary to develop methodologies to formulate these radiotherapeutic agents indigenously in our country. However, the challenges to prepare radiolabeled peptides in clinical-scale are manifold as these agents are required to be prepared with high specific activity using the 177 Lu, produced in our medium flux research reactor, for obtaining the desired therapeutic efficacy. In the past few years, methodologies for the formulation of clinical-scale 177 Lu-labelled peptides, suitable for human administration, have been developed in our facility and successfully translated to nuclear medicine centers of India, where these agents are regularly used for providing the radiotherapeutic treatment to the cancer patients.The presentation will describe our effort in successfully translating these agents from laboratory to nuclear medicine clinics and cover the aspects related to the development, demonstration and deployment of the radiolabeled

  11. Comprehensive computational design of ordered peptide macrocycles

    Science.gov (United States)

    Hosseinzadeh, Parisa; Bhardwaj, Gaurav; Mulligan, Vikram Khipple; Shortridge, Matthew D.; Craven, Timothy W.; Pardo-Avila, Fátima; Rettie, Stephen A.; Kim, David E.; Silva, Daniel-Adriano; Ibrahim, Yehia M.; Webb, Ian K.; Cort, John R.; Adkins, Joshua N.; Varani, Gabriele; Baker, David

    2018-01-01

    Mixed-chirality peptide macrocycles such as cyclosporine are among the most potent therapeutics identified to date, but there is currently no way to systematically search the structural space spanned by such compounds. Natural proteins do not provide a useful guide: Peptide macrocycles lack regular secondary structures and hydrophobic cores, and can contain local structures not accessible with L-amino acids. Here, we enumerate the stable structures that can be adopted by macrocyclic peptides composed of L- and D-amino acids by near-exhaustive backbone sampling followed by sequence design and energy landscape calculations. We identify more than 200 designs predicted to fold into single stable structures, many times more than the number of currently available unbound peptide macrocycle structures. Nuclear magnetic resonance structures of 9 of 12 designed 7- to 10-residue macrocycles, and three 11- to 14-residue bicyclic designs, are close to the computational models. Our results provide a nearly complete coverage of the rich space of structures possible for short peptide macrocycles and vastly increase the available starting scaffolds for both rational drug design and library selection methods. PMID:29242347

  12. Accurate prediction of peptide binding sites on protein surfaces.

    Directory of Open Access Journals (Sweden)

    Evangelia Petsalaki

    2009-03-01

    Full Text Available Many important protein-protein interactions are mediated by the binding of a short peptide stretch in one protein to a large globular segment in another. Recent efforts have provided hundreds of examples of new peptides binding to proteins for which a three-dimensional structure is available (either known experimentally or readily modeled but where no structure of the protein-peptide complex is known. To address this gap, we present an approach that can accurately predict peptide binding sites on protein surfaces. For peptides known to bind a particular protein, the method predicts binding sites with great accuracy, and the specificity of the approach means that it can also be used to predict whether or not a putative or predicted peptide partner will bind. We used known protein-peptide complexes to derive preferences, in the form of spatial position specific scoring matrices, which describe the binding-site environment in globular proteins for each type of amino acid in bound peptides. We then scan the surface of a putative binding protein for sites for each of the amino acids present in a peptide partner and search for combinations of high-scoring amino acid sites that satisfy constraints deduced from the peptide sequence. The method performed well in a benchmark and largely agreed with experimental data mapping binding sites for several recently discovered interactions mediated by peptides, including RG-rich proteins with SMN domains, Epstein-Barr virus LMP1 with TRADD domains, DBC1 with Sir2, and the Ago hook with Argonaute PIWI domain. The method, and associated statistics, is an excellent tool for predicting and studying binding sites for newly discovered peptides mediating critical events in biology.

  13. Proinsulin C-peptide interferes with insulin fibril formation

    International Nuclear Information System (INIS)

    Landreh, Michael; Stukenborg, Jan-Bernd; Willander, Hanna; Söder, Olle; Johansson, Jan; Jörnvall, Hans

    2012-01-01

    Highlights: ► Insulin and C-peptide can interact under insulin fibril forming conditions. ► C-peptide is incorporated into insulin aggregates and alters aggregation lag time. ► C-peptide changes insulin fibril morphology and affects backbone accessibility. ► C-peptide may be a regulator of fibril formation by β-cell granule proteins. -- Abstract: Insulin aggregation can prevent rapid insulin uptake and cause localized amyloidosis in the treatment of type-1 diabetes. In this study, we investigated the effect of C-peptide, the 31-residue peptide cleaved from proinsulin, on insulin fibrillation at optimal conditions for fibrillation. This is at low pH and high concentration, when the fibrils formed are regular and extended. We report that C-peptide then modulates the insulin aggregation lag time and profoundly changes the fibril appearance, to rounded clumps of short fibrils, which, however, still are Thioflavine T-positive. Electrospray ionization mass spectrometry also indicates that C-peptide interacts with aggregating insulin and is incorporated into the aggregates. Hydrogen/deuterium exchange mass spectrometry further reveals reduced backbone accessibility in insulin aggregates formed in the presence of C-peptide. Combined, these effects are similar to those of C-peptide on islet amyloid polypeptide fibrillation and suggest that C-peptide has a general ability to interact with amyloidogenic proteins from pancreatic β-cell granules. Considering the concentrations, these peptide interactions should be relevant also during physiological secretion, and even so at special sites post-secretory or under insulin treatment conditions in vivo.

  14. Synthesis of Thermoresponsive Amphiphilic Polyurethane Gel as a New Cell Printing Material near Body Temperature.

    Science.gov (United States)

    Tsai, Yi-Chun; Li, Suming; Hu, Shiaw-Guang; Chang, Wen-Chi; Jeng, U-Ser; Hsu, Shan-hui

    2015-12-23

    Waterborne polyurethane (PU) based on poly(ε-caprolactone) (PCL) diol and a second oligodiol containing amphiphilic blocks was synthesized in this study. The microstructure was characterized by dynamic light scattering (DLS), small-angle X-ray scattering (SAXS), and rheological measurement of the PU dispersion. The surface hydrophilicity measurement, infrared spectroscopy, wide-angle X-ray diffraction, mechanical and thermal analyses were conducted in solid state. It was observed that the presence of a small amount of amphiphilic blocks in the soft segment resulted in significant changes in microstructure. When 90 mol % PCL diol and 10 mol % amphiphilic blocks of poly(l-lactide)-poly(ethylene oxide) (PLLA-PEO) diol were used as the soft segment, the synthesized PU had a water contact angle of ∼24° and degree of crystallinity of ∼14%. The dispersion had a low viscosity below room temperature. As the temperature was raised to body temperature (37 °C), the dispersion rapidly (∼170 s) underwent sol-gel transition with excellent gel modulus (G' ≈ 6.5 kPa) in 20 min. PU dispersions with a solid content of 25-30% could be easily mixed with cells in sol state, extruded by a 3D printer, and deposited layer by layer as a gel. Cells remained alive and proliferating in the printed hydrogel scaffold. We expect that the development of novel thermoresponsive PU system can be used as smart injectable hydrogel and applied as a new type of bio-3D printing ink.

  15. Emergent properties arising from the assembly of amphiphiles. Artificial vesicle membranes as reaction promoters and regulators.

    Science.gov (United States)

    Walde, Peter; Umakoshi, Hiroshi; Stano, Pasquale; Mavelli, Fabio

    2014-09-14

    This article deals with artificial vesicles and their membranes as reaction promoters and regulators. Among the various molecular assemblies which can form in an aqueous medium from amphiphilic molecules, vesicle systems are unique. Vesicles compartmentalize the aqueous solution in which they exist, independent on whether the vesicles are biological vesicles (existing in living systems) or whether they are artificial vesicles (formed in vitro from natural or synthetic amphiphiles). After the formation of artificial vesicles, their aqueous interior (the endovesicular volume) may become - or may be made - chemically different from the external medium (the exovesicular solution), depending on how the vesicles are prepared. The existence of differences between endo- and exovesicular composition is one of the features on the basis of which biological vesicles contribute to the complex functioning of living organisms. Furthermore, artificial vesicles can be formed from mixtures of amphiphiles in such a way that the vesicle membranes become molecularly, compositionally and organizationally highly complex, similarly to the lipidic matrix of biological membranes. All the various properties of artificial vesicles as membranous compartment systems emerge from molecular assembly as these properties are not present in the individual molecules the system is composed of. One particular emergent property of vesicle membranes is their possible functioning as promoters and regulators of chemical reactions caused by the localization of reaction components, and possibly catalysts, within or on the surface of the membranes. This specific feature is reviewed and highlighted with a few selected examples which range from the promotion of decarboxylation reactions, the selective binding of DNA or RNA to suitable vesicle membranes, and the reactivation of fragmented enzymes to the regulation of the enzymatic synthesis of polymers. Such type of emergent properties of vesicle membranes may

  16. A Review of the Role of Amphiphiles in Biomass to Ethanol Conversion

    Directory of Open Access Journals (Sweden)

    William Gibbons

    2013-04-01

    Full Text Available One of the concerns for economical production of ethanol from biomass is the large volume and high cost of the cellulolytic enzymes used to convert biomass into fermentable sugars. The presence of acetyl groups in hemicellulose and lignin in plant cell walls reduces accessibility of biomass to the enzymes and makes conversion a slow process. In addition to low enzyme accessibility, a rapid deactivation of cellulases during biomass hydrolysis can be another factor contributing to the low sugar recovery. As of now, the economical reduction in lignin content of the biomass is considered a bottleneck, and raises issues for several reasons. The presence of lignin in biomass reduces the swelling of cellulose fibrils and accessibility of enzyme to carbohydrate polymers. It also causes an irreversible adsorption of the cellulolytic enzymes that prevents effective enzyme activity and recycling. Amphiphiles, such as surfactants and proteins have been found to improve enzyme activity by several mechanisms of action that are not yet fully understood. Reduction in irreversible adsorption of enzyme to non-specific sites, reduction in viscosity of liquid and surface tension and consequently reduced contact of enzyme with air-liquid interface, and modifications in biomass chemical structure are some of the benefits derived from surface active molecules. Application of some of these amphiphiles could potentially reduce the capital and operating costs of bioethanol production by reducing fermentation time and the amount of enzyme used for saccharification of biomass. In this review article, the benefit of applying amphiphiles at various stages of ethanol production (i.e., pretreatment, hydrolysis and hydrolysis-fermentation is reviewed and the proposed mechanisms of actions are described.

  17. Effective lubrication of articular cartilage by an amphiphilic hyaluronic acid derivative.

    Science.gov (United States)

    Schiavinato, Antonella; Whiteside, Robert A

    2012-06-01

    Intra-articular injection of hyaluronic acid based therapies is gaining popularity as a treatment option for non-operative management of patients with symptomatic osteoarthritis. Although there is an abundance of evidence for both biological and mechanical mechanisms of joint protection by hyaluronic acid, one clear intention of viscosupplementation is to reduce friction and wear by providing an extrinsic lubricant. We tested the in vitro friction response of a novel hyaluronic acid derivative that presents amphiphilic features to promote adhesion to the cartilage surface and thereby improve cartilage lubrication. Migrating Contact Area and Static Contact Area friction tests were conducted on bovine articular cartilage to assess the efficacy of two lubricants, a chemically modified amphiphilic hyaluronic acid and synovial fluid from a healthy joint, as well as a phosphate buffered saline negative control. No differences in lubrication (P=0.34) were evident between the three test articles during the Migrating Contact Area test, which represents articulation of healthy articular cartilage. The modified hyaluronic acid presented an equilibrium friction coefficient 2.8 times less than that of the synovial fluid (P ≤ 0.0005) and five times less than that of the PBS control (P ≤ 0.0001) during the Static Contact Area test, representing a mixed lubrication condition. The present study demonstrated that a chemically modified amphiphilic hyaluronic acid can provide equivalent lubrication to synovial fluid during articulation of loaded healthy articular cartilage and can provide superior lubrication as indicated by a lower coefficient of friction than synovial fluid under loading conditions potentially associated with cartilage wear. Copyright © 2011 Elsevier Ltd. All rights reserved.

  18. Preparation and morphology control of amphiphilic block copolymer thin films using mixed solvent vapors

    Energy Technology Data Exchange (ETDEWEB)

    Xie, Chan, E-mail: xiechan@pku.edu.cn [Beijing National Laboratory for Molecular Sciences, Key Laboratory of Polymer Chemistry and Physics of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871 (China); School of Material Science and Engineering, Nanchang Hangkong University, Jiangxi, Nanchang, 330063 (China); Zhou, Yu; Zhou, Feng; Wu, Hongwei; Zou, Dechun; Fan, Xinghe [Beijing National Laboratory for Molecular Sciences, Key Laboratory of Polymer Chemistry and Physics of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871 (China); Shen, Zhihao, E-mail: zshen@pku.edu.cn [Beijing National Laboratory for Molecular Sciences, Key Laboratory of Polymer Chemistry and Physics of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871 (China)

    2014-03-01

    Graphical abstract: A series of well-defined amphiphilic block copolymer (BCP), poly[N,N-(dimethylamino)ethyl methacrylate]-block-polystyrene (PDMAEMA-b-PS), was synthesized using the ARGET ATRP method. Solvent annealing was applied for controlling the thin-film morphologies. A vertical nanocylinder structure forms in the thin film annealed under the vapors of binary mixed solvents from water and tetrahydrofuran which have a strong selectivity for the minority PDMAEMA block. - Highlights: • Well-defined amphiphilic diblock copolymers synthesized. • Systematic study on morphologies in thin films controlled by annealing under vapors of mixed solvents. - Abstract: A well-defined amphiphilic diblock copolymer, poly[N,N-(dimethylamino)ethyl methacrylate]-block-polystyrene (PDMAEMA-b-PS), was synthesized using activators regenerated by electron transfer atom transfer radical polymerization. The formation and transition of morphologies in PDMAEMA-b-PS thin films annealed under the vapors of water, tetrahydrofuran, and their binary mixed solvents were first investigated by using atomic force microscopy and scanning electron microscopy. By changing the composition of the annealing solvent, morphological evolution with increasing vapor preferential affinity was observed. A vertical nanocylinder structure forms in the PDMAEMA-b-PS thin film when it is annealed under a mixed solvent vapor with Δχ ∼ −0.975 having a strong preferential affinity for the minority PDMAEMA block at ambient temperature. The self-assembly of PDMAEMA-b-PS thin films provides a new convenient way to fabricate stimuli-responsive substrates with potential applications in adhesion control, wetting, and binding or release of functional molecules at surfaces.

  19. Functional Hybrid Biomaterials based on Peptide-Polymer Conjugates for Nanomedicine

    Science.gov (United States)

    Shu, Jessica Yo

    The focus of this dissertation is the design, synthesis and characterization of hybrid functional biomaterials based on peptide-polymer conjugates for nanomedicine. Generating synthetic materials with properties comparable to or superior than those found in nature has been a "holy grail" for the materials community. Man-made materials are still rather simplistic when compared to the chemical and structural complexity of a cell. Peptide-polymer conjugates have the potential to combine the advantages of the biological and synthetic worlds---that is they can combine the precise chemical structure and diverse functionality of biomolecules with the stability and processibility of synthetic polymers. As a new family of soft matter, they may lead to materials with novel properties that have yet to be realized with either of the components alone. In order for peptide-polymer conjugates to reach their full potential as useful materials, the structure and function of the peptide should be maintained upon polymer conjugation. The success in achieving desirable, functional assemblies relies on fundamentally understanding the interactions between each building block and delicately balancing and manipulating these interactions to achieve targeted assemblies without interfering with designed structures and functionalities. Such fundamental studies of peptide-polymer interactions were investigated as the nature of the polymer (hydrophilic vs. hydrophobic) and the site of its conjugation (end-conjugation vs. side-conjugation) were varied. The fundamental knowledge gained was then applied to the design of amphiphiles that self-assemble to form stable functional micelles. The micelles exhibited exceptional monodispersity and long-term stability, which is atypical of self-assembled systems. Thus such micelles based on amphiphilic peptide-polymer conjugates may meet many current demands in nanomedicine, in particular for drug delivery of hydrophobic anti-cancer therapeutics. Lastly

  20. Small angle neutron scattering study of the micelle structure of amphiphilic block copolymers

    International Nuclear Information System (INIS)

    Yamaoka, H.; Matsuoka, H.; Sumaru, K.; Hanada, S.

    1994-01-01

    The amphiphilic block copolymers of vinyl ether were prepared by living cationic polymerization. The partially deuterated copolymers for SANS experiments were especially synthesized by introducing deuterated phenyl units in the hydrophobic chain. SANS measurements were performed for aqueous solutions of these copolymers by changing H 2 O/D 2 O ratios. The SANS profiles indicate that the micelles in the present system exhibit a core-shell structure and that the size and shape of micelles are largely dependent on the length of hydrophobic chain. The micelle of shorter hydrophobic chain was found to be nearly spherical, whereas the micelle of longer hydrophobic chain was confirmed to have an ellipsoidal shape

  1. Interactions between colloidal particles in the presence of an ultrahighly charged amphiphilic polyelectrolyte.

    Science.gov (United States)

    Yu, Danfeng; Yang, Hui; Wang, Hui; Cui, Yingxian; Yang, Guang; Zhang, Jian; Wang, Jinben

    2014-12-09

    A novel amphiphilic polyelectrolyte denoted as PAGC8 and a traditional amphiphilic polyelectrolyte denoted as PASC8 were prepared. PAGC8 consisted of gemini-type surfactant segment based on 1,3-bis (N,N-dimethyl-N-octylammonium)-2-propyl acrylate dibromide, while PASC8 incorporated acryloyloxyethyl-N,N-dimethyl-N-dodecylammonium bromide as single chain surfactant units within its repeat unit structure. Turbidity, stability, and zeta potential measurements were performed in the presence of PAGC8 and PASC8, respectively, to evaluate their effectiveness in inducing solid/liquid separations. It was found that the maximum transmittance was observed before the zeta potential values reached the isoelectric point, implying that not only charge neutralization but also charge-patch mechanism contributed to the separation process. Colloid probe atomic force microscopy technique was introduced to directly determine the interactions between surfaces in the presence of ultrahighly charged amphiphilic polyelectrolyte. On the basis of the AFM results, we have successfully interpreted the influence of the charge density of the polyelectrolytes on the phase stability. Electrostatic interaction played the dominant role in the flocculation processes, although both electrostatic interaction and hydrophobic effect provided contributions to the colloidal dispersions. The attractions upon surfaces approach in the case of PAGC8 were significantly larger than that of PASC8 due to the higher charge density. The strong peeling events upon retraction in the presence of PAGC8 implied that the hydrophobic effect was stronger than that of PASC8, which displayed the loose pulling events. A strong attraction was identified at shorter separation distances for both systems. However, these interactions cannot be successfully described by the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory of colloid stability due to the participation of charge-patch and strong hydrophobic effect. To account for the

  2. Synthesis of Novel Amphiphilic Azobenzenes and X-ray Scattering Studies of Their Langmuir Monolayers

    DEFF Research Database (Denmark)

    Sørensen, Thomas Just; Kjær, Kristian; Breiby, Dag Werner

    2008-01-01

    . At the air-water interface, the amphiphilic azobenzenes form noncrystalline but stable Langmuir films that display an unusual reversible monolayer collapse close to 35 mN/m. The structures and phase transitions were studied by X-ray reflectivity (XR) and grazing-incidence X-ray diffraction, both utilizing...... synchrotron radiation. Compression beyond the collapse point does not change the XR data, showing that the film is unchanged at the molecular level, even at areas less than half of that of the collapse. This leads to the conclusion that few macroscopic collapse sites are responsible for reversibly removing...

  3. Macroscopic alignment of graphene stacks by Langmuir-Blodgett deposition of amphiphilic hexabenzocoronenes

    DEFF Research Database (Denmark)

    Laursen, B.W.; Nørgaard, K.; Reitzel, N.

    2004-01-01

    e present structural studies of Langmuir V and Langmuir-Blodgett (LB) films of new amphiphilic hexa-peri-hexabenzocoronene (HBC) discotics, carrying five branched alkyl side chains and one polar group. The polar group is either a carboxylic acid moiety or an electron acceptor moiety (anthraquinone...... and tilted relative to the water surface. The intercolumnar distance is 20 A. The HBCs are confined to a layer lying on top of the layer of polar groups that are in contact with the water subphase. Efficient transfer of the monolayer of the anthraquinone-substituted HBC derivative to hydrophobic quartz...

  4. A spectroscopic method to estimate the binding potency of amphiphile assemblies

    Czech Academy of Sciences Publication Activity Database

    Gauger, D. R.; Andrushchenko, Valery; Bouř, Petr; Pohle, W.

    2010-01-01

    Roč. 398, č. 2 (2010), s. 1109-1123 ISSN 1618-2642 R&D Projects: GA ČR GA203/06/0420; GA ČR GA202/07/0732; GA ČR GAP208/10/0559; GA AV ČR IAA400550702; GA AV ČR IAA400550701 Institutional research plan: CEZ:AV0Z40550506 Keywords : miccels * amphiphile assemblies * molecular dynamics * infrared spectroscopy Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.841, year: 2010

  5. Short stature

    Science.gov (United States)

    ... as her parents. Providers call this "constitutional growth delay." If one or both parents are short, your ... urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows ...

  6. SHORT COMMUNICATION

    African Journals Online (AJOL)

    PROF P.T. KAYE

    . SHORT COMMUNICATION. Formation and Structural Analysis of Novel Dibornyl Ethers. Perry T. Kaye*, Andrew R. Duggan, Joseph M. Matjila, Warner E. Molema, and. Swarnam S. Ravindran. Department of Chemistry, Rhodes University, Grahamstown, ...

  7. Catalytic Y-tailed amphiphilic homopolymers – aqueous nanoreactors for high activity, low loading SCS pincer catalysts

    Science.gov (United States)

    Patterson, Joseph P.; Cotanda, Pepa; Kelley, Elizabeth G.; Moughton, Adam O.; Lu, Annhelen; Epps, Thomas H.; O’Reilly, Rachel K.

    2013-01-01

    A new amphiphilic homopolymer bearing an SCS pincer palladium complex has been synthesized by reversible addition fragmentation chain transfer polymerization. The amphiphile has been shown to form spherical and worm-like micelles in water by cryogenic transmission electron microscopy and small angle neutron scattering. Segregation of reactive components within the palladium containing core results in increased catalytic activity of the pincer compound compared to small molecule analogues. This allows carbon-carbon bond forming reactions to be performed in water with reduced catalyst loadings and enhanced activity. PMID:23539324

  8. Interpretation of Tandem Mass Spectrometry (MSMS) Spectra for Peptide Analysis

    DEFF Research Database (Denmark)

    Hjernø, Karin; Højrup, Peter

    2015-01-01

    The aim of this chapter is to give a short introduction to peptide analysis by mass spectrometry (MS) and interpretation of fragment mass spectra. Through examples and guidelines we demonstrate how to understand and validate search results and how to perform de novo sequencing based on the often...... very complex fragmentation pattern obtained by tandem mass spectrometry (also referred to as MSMS). The focus is on simple rules for interpretation of MSMS spectra of tryptic as well as non-tryptic peptides....

  9. What can machine learning do for antimicrobial peptides, and what can antimicrobial peptides do for machine learning?

    Science.gov (United States)

    Lee, Ernest Y; Lee, Michelle W; Fulan, Benjamin M; Ferguson, Andrew L; Wong, Gerard C L

    2017-12-06

    Antimicrobial peptides (AMPs) are a diverse class of well-studied membrane-permeating peptides with important functions in innate host defense. In this short review, we provide a historical overview of AMPs, summarize previous applications of machine learning to AMPs, and discuss the results of our studies in the context of the latest AMP literature. Much work has been recently done in leveraging computational tools to design new AMP candidates with high therapeutic efficacies for drug-resistant infections. We show that machine learning on AMPs can be used to identify essential physico-chemical determinants of AMP functionality, and identify and design peptide sequences to generate membrane curvature. In a broader scope, we discuss the implications of our findings for the discovery of membrane-active peptides in general, and uncovering membrane activity in new and existing peptide taxonomies.

  10. Descriptors for antimicrobial peptides

    DEFF Research Database (Denmark)

    Jenssen, Håvard

    2011-01-01

    Introduction: A frightening increase in the number of isolated multidrug resistant bacterial strains linked to the decline in novel antimicrobial drugs entering the market is a great cause for concern. Cationic antimicrobial peptides (AMPs) have lately been introduced as a potential new class...... of antimicrobial drugs, and computational methods utilizing molecular descriptors can significantly accelerate the development of new peptide drug candidates. Areas covered: This paper gives a broad overview of peptide and amino-acid scale descriptors available for AMP modeling and highlights which...

  11. Peptides in headlock ? a novel high-affinity and versatile peptide-binding nanobody for proteomics and microscopy

    OpenAIRE

    Braun, Michael B.; Traenkle, Bjoern; Koch, Philipp A.; Emele, Felix; Weiss, Frederik; Poetz, Oliver; Stehle, Thilo; Rothbauer, Ulrich

    2016-01-01

    Nanobodies are highly valuable tools for numerous bioanalytical and biotechnical applications. Here, we report the characterization of a nanobody that binds a short peptide epitope with extraordinary affinity. Structural analysis reveals an unusual binding mode where the extended peptide becomes part of a ?-sheet structure in the nanobody. This interaction relies on sequence-independent backbone interactions augmented by a small number of specificity-determining side chain contacts. Once boun...

  12. Synthesis of an amphiphilic rhodamine derivative and characterization of its solution and thin film properties

    Energy Technology Data Exchange (ETDEWEB)

    Aviv, Hagit [Department of Chemistry, Bar-Ilan University, Ramat-Gan (Israel); Bar-Ilan University Institute for Nanotechnology and Advanced Materials, Ramat-Gan (Israel); Harazi, Sivan [Department of Chemistry, Bar-Ilan University, Ramat-Gan (Israel); Department of Physics, Bar-Ilan University, Ramat-Gan (Israel); Bar-Ilan University Institute for Nanotechnology and Advanced Materials, Ramat-Gan (Israel); Schiff, Dillon [Department of Chemistry, Bar-Ilan University, Ramat-Gan (Israel); Bar-Ilan University Institute for Nanotechnology and Advanced Materials, Ramat-Gan (Israel); Ramon, Yoni [Department of Chemistry, Bar-Ilan University, Ramat-Gan (Israel); Department of Physics, Bar-Ilan University, Ramat-Gan (Israel); Bar-Ilan University Institute for Nanotechnology and Advanced Materials, Ramat-Gan (Israel); Tischler, Yaakov R., E-mail: yrt@biu.ac.il [Department of Chemistry, Bar-Ilan University, Ramat-Gan (Israel); Bar-Ilan University Institute for Nanotechnology and Advanced Materials, Ramat-Gan (Israel)

    2014-08-01

    Here we present characterization of solution and thin film properties of Lissamine rhodamine B sulfonyl didodecyl amine (LRSD), an amphiphilic derivative of rhodamine. LRSD was synthesized by functionalizing Lissamine rhodamine B sulfonyl chloride (LRSC) with didodecylamine via a straightforward sulfonylation reaction. LRSD's long alkane chains make it highly soluble in chloroform, with a marked increase in brightness compared to the starting material. LRSD is shown to form well-defined robust micelles in water, without the addition of a co-surfactant and stable monolayers at the air–water interface. The greater lipophilicity of LRSD also enables doping into non-polar polymeric host matrices such as polystyrene with less aggregation and hence higher fluorescence quantum yield than LRSC or even rhodamine B. The monolayers of LRSD were prepared via Langmuir–Blodgett deposition and showed shifts in the photoluminescence peak from 575 nm to 595 nm, as the surface pressure is varied from 3 mN/m to 11 mN/m. - Highlights: • Lissamine rhodamine B sulfonyl didodecyl amine (LRSD) is soluble in chloroform. • LRSD shows robust quantum yield in solution and as a dopant in thin film. • LRSD is an amphiphilic rhodamine dye that forms compact fluorescent micelles. • LRSD forms a stable isotherm when spread at the air–water interface.

  13. Amphiphilic block copolymer/poly(dimethylsiloxane) (PDMS) blends and nanocomposites for improved fouling-release.

    Science.gov (United States)

    Martinelli, Elisa; Suffredini, Marianna; Galli, Giancarlo; Glisenti, Antonella; Pettitt, Michala E; Callow, Maureen E; Callow, James A; Williams, David; Lyall, Graeme

    2011-05-01

    Amphiphilic diblock copolymers, Sz6 and Sz12, consisting of a poly(dimethylsiloxane) block (average degree of polymerisation = 132) and a PEGylated-fluoroalkyl modified polystyrene block (Sz, average degree of polymerisation = 6, 12) were prepared by atom transfer radical polymerization (ATRP). Coatings were obtained from blends of either block copolymer (1-10 wt%) with a poly(dimethylsiloxane) (PDMS) matrix. The coating surface presented a simultaneous hydrophobic and lipophobic character, owing to the strong surface segregation of the lowest surface energy fluoroalkyl chains of the block copolymer. Surface chemical composition and wettability of the films were affected by exposure to water. Block copolymer Sz6 was also blended with PDMS and a 0.1 wt% amount of multiwall carbon nanotubes (CNT). The excellent fouling-release (FR) properties of these new coatings against the macroalga Ulva linza essentially resulted from the inclusion of the amphiphilic block copolymer, while the addition of CNT did not appear to improve the FR properties.

  14. Self-assembly of crystalline nanotubes from monodisperse amphiphilic diblock copolypeptoid tiles.

    Science.gov (United States)

    Sun, Jing; Jiang, Xi; Lund, Reidar; Downing, Kenneth H; Balsara, Nitash P; Zuckermann, Ronald N

    2016-04-12

    The folding and assembly of sequence-defined polymers into precisely ordered nanostructures promises a class of well-defined biomimetic architectures with specific function. Amphiphilic diblock copolymers are known to self-assemble in water to form a variety of nanostructured morphologies including spheres, disks, cylinders, and vesicles. In all of these cases, the predominant driving force for assembly is the formation of a hydrophobic core that excludes water, whereas the hydrophilic blocks are solvated and extend into the aqueous phase. However, such polymer systems typically have broad molar mass distributions and lack the purity and sequence-defined structure often associated with biologically derived polymers. Here, we demonstrate that purified, monodisperse amphiphilic diblock copolypeptoids, with chemically distinct domains that are congruent in size and shape, can behave like molecular tile units that spontaneously assemble into hollow, crystalline nanotubes in water. The nanotubes consist of stacked, porous crystalline rings, and are held together primarily by side-chain van der Waals interactions. The peptoid nanotubes form without a central hydrophobic core, chirality, a hydrogen bond network, and electrostatic or π-π interactions. These results demonstrate the remarkable structure-directing influence of n-alkane and ethyleneoxy side chains in polymer self-assembly. More broadly, this work suggests that flexible, low-molecular-weight sequence-defined polymers can serve as molecular tile units that can assemble into precision supramolecular architectures.

  15. Controlled synthesis of CeO2 nanoparticles using novel amphiphilic cerium complex precursors

    International Nuclear Information System (INIS)

    Yan Bing; Zhu Hongxia

    2008-01-01

    Maleic anhydride was grafted by long-chain alcohols (1-hexadecanol, 1-octadecanol) to amphiphilic mono-L cis-butene dicarboxylates (L = hexadecyl, octadecyl), i.e., MAH, MAO, respectively. Subsequently, corresponding amphiphilic cerium complexes with these two mono-L cis-butene dicarboxylate ligands (Ce(L') 3 , L'= MAH, MAO) were synthesized and behaved as the precursors to prepare CeO 2 nanoparticles for both of which can form nanosized micelle-like aggregates by special self-assembly in the wet chemical process. The nanoparticles were further characterized by Fourier transform-infrared spectroscopy (FTIR), Diffuse reflectance ultraviolet-visible spectra (DRUVS), scanning electron microscope (SEM), transmission electron microscope (TEM), and x-ray diffraction (XRD). Both the CeO 2 nanoparticles are in a cubic fluorite structure and present regular and well-dispersion club-like morphology with average particle size in the range of 40-70 nm. Besides, the strong ultraviolet-visible absorption for these CeO 2 nanoparticles can be found at the long-wavelength ultraviolet to visible region of 200-500 nm.

  16. Macromolecules with amphiphilic monomer units at interface of two immiscible liquids

    Science.gov (United States)

    Glagoleva, A. A.; Vasilevskaya, V. V.

    2017-11-01

    The adsorption of macromolecules with amphiphilic monomer units at the liquid-liquid interface was studied. The amphiphilic structure of monomer units with groups selectively interacting with α and β liquids was described by the A-graft-B dumbbell model. The calculations were performed for the symmetrical interaction of A and B groups with liquids, different selectivity parameters ξ and degree of polymerization N. The simulations indicate a three-step adsorption scenario, including non-adsorbed, weak and strong localization states. It was shown that the adsorption of (A-graft-B)N macromolecules obeys scaling laws developed to describe the adsorption of the alternating (AB)N copolymer at the liquid-liquid interface with critical selectivity parameter ξc of transition into the weak localization state depending on the degree of polymerization as N-1/5; critical selectivity parameter ξ∞ of transition to the strong localization regime non-depending on the degree of polymerization; and relative change of perpendicular Rz radius of gyration varying as a power function of ξN1/5: Rz(ξ)/Rz(0) ˜ (ξN1/5)ρ and ρ = -2ν/(1 - v). Meanwhile, (A-graft-B)N macromolecules have much lower ξc and ξ∞ values and thus are more prospective for practical applications.

  17. Hydration-Induced Phase Separation in Amphiphilic Polymer Matrices and its Influence on Voclosporin Release

    Directory of Open Access Journals (Sweden)

    Joachim Kohn

    2012-10-01

    Full Text Available Voclosporin is a highly potent, new cyclosporine-A derivative that is currently in Phase 3 clinical trials in the USA as a potential treatment for inflammatory diseases of the eye. Voclosporin represents a number of very sparingly soluble drugs that are difficult to administer. We therefore selected it as a model drug that is dispersed within amphiphilic polymer matrices, and investigated the changing morphology of the matrices using neutron and x-ray scattering during voclosporin release and polymer resorption. The hydrophobic segments of the amphiphilic polymer chain are comprised of desaminotyrosyl-tyrosine ethyl ester (DTE and desaminotyrosyl-tyrosine (DT, and the hydrophilic component is poly(ethylene glycol (PEG. Water uptake in these matrices resulted in the phase separation of hydrophobic and hydrophilic domains that are a few hundred Angstroms apart. These water-driven morphological changes influenced the release profile of voclosporin and facilitated a burst-free release from the polymer. No such morphological reorganization was observed in poly(lactide-co-glycolide (PLGA, which exhibits an extended lag period, followed by a burst-like release of voclosporin when the polymer was degraded. An understanding of the effect of polymer composition on the hydration behavior is central to understanding and controlling the phase behavior and resorption characteristics of the matrix for achieving long-term controlled release of hydrophobic drugs such as voclosporin.

  18. Polydispersity-Driven Block Copolymer Amphiphile Self-Assembly into Prolate-Spheroid Micelles

    Energy Technology Data Exchange (ETDEWEB)

    Schmitt, Andrew L.; Repollet-Pedrosa, Milton H.; Mahanthappa, Mahesh K. (UW)

    2013-09-26

    The aqueous self-assembly behavior of polydisperse poly(ethylene oxide-b-1,4-butadiene-b-ethylene oxide) (OBO) macromolecular triblock amphiphiles is examined to discern the implications of continuous polydispersity in the hydrophobic block on the resulting aqueous micellar morphologies of otherwise monodisperse polymer surfactants. The chain length polydispersity and implicit composition polydispersity of these samples furnishes a distribution of preferred interfacial curvatures, resulting in dilute aqueous block copolymer dispersions exhibiting coexisting spherical and rod-like micelles with vesicles in a single sample with a O weight fraction, w{sub O}, of 0.18. At higher w{sub O} = 0.51-0.68, the peak in the interfacial curvature distribution shifts and we observe the formation of only American football-shaped micelles. We rationalize the formation of these anisotropically shaped aggregates based on the intrinsic distribution of preferred curvatures adopted by the polydisperse copolymer amphiphiles and on the relief of core block chain stretching by chain-length-dependent intramicellar segregation.

  19. Amphiphilic nanosheet self-assembly at the water/oil interface: computer simulations.

    Science.gov (United States)

    Xiang, Wenjun; Zhao, Shuangliang; Song, Xianyu; Fang, Shenwen; Wang, Fen; Zhong, Cheng; Luo, Zhaoyang

    2017-03-15

    In this paper, dissipative particle dynamics simulations are performed to study the interfacial and emulsion stabilizing properties of various systems of amphiphilic nanosheets (ANs) self-assembled at the oil/water (O/W) interface. The ANs have a dimensional symmetry structure that encompasses a triangular-plate at the center and two soft comb-like shells constructed with hydrophilic and hydrophobic polymers. As the simulation results show, the AN molecules are highly oriented in interfacial films with their triangular nanosheets parallel to the O/W interface, while their hydrophobic and hydrophilic segments attempt to immerse into the oil phase and aqueous phase, respectively. These results reveal that the rotation of ANs at oil/water interfaces is greatly restricted, meanwhile, their nanosheet (or planar) configuration facilitates their favorable orientation thereby, thus making the emulsion more stable. At higher concentrations, a wrapped-like or micelle morphology is observed. The O/W emulsions stabilized by ANs were also simulated, and it is interesting to find AN 'patches' at the O/W interface which resembles the leather patches on a football. By introducing the "amphiphilic nanosheet balance" concept, the hydrophilic-lipophilic balance (HLB) values of ANs were calculated. Due to their properties of two-dimensional symmetry, the HLB values of ANs tend to approximately 1 which reveals a stronger stability for emulsions.

  20. Dilational rheology of oil/water interfaces covered by amphiphilic polysaccharides derived from dextran.

    Science.gov (United States)

    Desbrières, Jacques; López-Gonzalez, Edeluc; Aguilera-Miguel, Antonio; Sadtler, Véronique; Marchal, Philippe; Castel, Christophe; Choplin, Lionel; Durand, Alain

    2017-12-01

    This work studied the adsorption at dodecane/water interface of amphiphilic polysaccharides derived from dextran (a nonionic bacterial polysaccharide) by random attachment of phenoxy groups along the chains (between 10 and 20 attached phenoxy groups per 100 glucose repeat units). The long-time kinetics of interfacial tension decrease was satisfactorily described assuming diffusion-limited adsorption of hydrophobic units (over 4h). Dilational rheology of dodecane/water interface was studied for the first time with that kind of amphiphilic polysaccharides and evidenced a significant elastic component. For all dextran derivatives, experimental results were conveniently described using Lucassen-van den Tempel model which assumed diffusion-limited of surface active species. The characteristic frequency increased with the number of attached phenoxy groups and its order of magnitude (10 -3 -10 -2 rad.s -1 ) was consistent with estimations based on the previous model. Experimental results were compared to those obtained with commercial stabilizers like Pluronics (L64, P105, F68 and F127) and Tween 80. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Amphiphilic copolymers reduce aggregation of unfolded lysozyme more effectively than polyethylene glycol

    Science.gov (United States)

    Chin, Jaemin; Mustafi, Devkumar; Poellmann, Michael J.; Lee, Raphael C.

    2017-02-01

    Certain amphiphilic block copolymers are known to prevent aggregation of unfolded proteins. To better understand the mechanism of this effect, the optical properties of heat-denatured and dithiothreitol reduced lysozyme were evaluated with respect to controls using UV-Vis spectroscopy, transmission electron microscopy (TEM) and circular dichroism (CD) measurements. Then, the effects of adding Polyethylene Glycol (8000 Da), the triblock surfactant Poloxamer 188 (P188), and the tetrablock copolymer Tetronic 1107 (T1107) to the lysozyme solution were compared. Overall, T1107 was found to be more effective than P188 in inhibiting aggregation, while PEG exhibited no efficacy. TEM imaging of heat-denatured and reduced lysozymes revealed spherical aggregates with on average 250-450 nm diameter. Using CD, more soluble lysozyme was recovered with T1107 than P188 with β-sheet secondary structure. The greater effectiveness of the larger T1107 in preventing aggregation of unfolded lysozyme than the smaller P188 and PEG points to steric hindrance at play; signifying the importance of size match between the hydrophobic region of denatured protein and that of amphiphilic copolymers. Thus, our results corroborate that certain multi-block copolymers are effective in preventing heat-induced aggregation of reduced lysozymes and future studies warrant more detailed focus on specific applications of these copolymers.

  2. Photoisomerization of amphiphilic azobenzene derivatives in Langmuir Blodgett films prepared as polyion complexes, using ionic polymers

    Energy Technology Data Exchange (ETDEWEB)

    Shembekar, Vishakha R. [Department of Chemistry, Indian Institute of Technology, Bombay, Mumbai-400 076 (India); Contractor, A.Q. [Department of Chemistry, Indian Institute of Technology, Bombay, Mumbai-400 076 (India); Major, S.S. [Department of Physics, Indian Institute of Technology, Bombay, Mumbai-400 076 (India); Talwar, S.S. [Department of Physics, Indian Institute of Technology, Bombay, Mumbai-400 076 (India)]. E-mail: chsstia@phy.iitb.ac.in.z

    2006-07-03

    Polyion complexation in mixed Langmuir and Langmuir Blodgett (LB) films of photochromic amphiphilic azobenzene carboxylic acids, 11-[4-(4-hexylphenyl)azo] phenoxyundecanoic acid, 11-(4-phenylazo)phenoxyundecanoic acid, and diamine grafted poly(methylmethaacrylate) polymers has been studied. Monolayer behaviour of the pure components and mixed films was studied through pressure-area isotherms and LB films were characterized by spectroscopic, X-ray diffraction and Atomic force microscopy techniques. Aggregation (H-type), often observed in LB films of pure amphiphilic azo acids, was partly avoided in the mixed LB films as indicated by absorption spectral studies. Photoisomerization of the polyion complexed LB films was also studied. The results altogether demonstrate that amine grafted polymer enter into a polyion complexation with azo acid carboxylate group. LB films could be obtained by transfer of the composite monolayers and these LB films exhibited different levels of aggregation of the azo acids. Reversible photoisomerization was observed in LB films with unaggregated azo acid.

  3. Amphiphilic nanoparticles suppress droplet break-up in a concentrated emulsion flowing through a narrow constriction.

    Science.gov (United States)

    Gai, Ya; Kim, Minkyu; Pan, Ming; Tang, Sindy K Y

    2017-05-01

    This paper describes the break-up behavior of a concentrated emulsion comprising drops stabilized by amphiphilic silica nanoparticles flowing in a tapered microchannel. Such geometry is often used in serial droplet interrogation and sorting processes in droplet microfluidics applications. When exposed to high viscous stresses, drops can undergo break-up and compromise their physical integrity. As these drops are used as micro-reactors, such compromise leads to a loss in the accuracy of droplet-based assays. Here, we show droplet break-up is suppressed by replacing the fluoro-surfactant similar to the one commonly used in current droplet microfluidics applications with amphiphilic nanoparticles as droplet stabilizer. We identify parameters that influence the break-up of these drops and demonstrate that break-up probability increases with increasing capillary number and confinement, decreasing nanoparticle size, and is insensitive to viscosity ratio within the range tested. Practically, our results reveal two key advantages of nanoparticles with direct applications to droplet microfluidics. First, replacing surfactants with nanoparticles suppresses break-up and increases the throughput of the serial interrogation process to 3 times higher than that in surfactant system under similar flow conditions. Second, the insensitivity of break-up to droplet viscosity makes it possible to process samples having different composition and viscosities without having to change the channel and droplet geometry in order to maintain the same degree of break-up and corresponding assay accuracy.

  4. Preparation and Microbiological Evaluation of Amphiphilic Kanamycin-Lipoamino Acid Ion-Pairs

    Directory of Open Access Journals (Sweden)

    Rosario Pignatello

    2014-05-01

    Full Text Available Amphiphilic ion-pairs of kanamycin (KAN were prepared by evaporation of a water-ethanol co-solution of KAN base and a lipoamino acid bearing a 12-carbon atoms alkyl side chain (LAA12, at different molar ratios. Infrared spectroscopy confirmed the structure of ion-pairs, while differential scanning calorimetry (DSC and powder X-ray diffractometry (PXRD studies supported the formation of new saline species with a different crystalline structure than the starting components. The solubility pattern shown in a range of both aqueous and organic solvents confirmed that the ion-pairs possess an amphiphilic character. The LAA12 counter-ion showed not to improve the antibacterial activity of KAN, suggesting that such chemical strategy is not able to favor the penetration of this drug inside the bacteria cells. Nevertheless, a slight improving, i.e., a one-fold dilution, was observed in E. coli. The present study can also serve as the basis for a further evaluation of LAA ion-pairing of antibiotics, as a means to improve the loading of hydrophilic drugs into lipid-based nanocarriers.

  5. Amphiphilic self-assembled polymeric copper catalyst to parts per million levels: click chemistry.

    Science.gov (United States)

    Yamada, Yoichi M A; Sarkar, Shaheen M; Uozumi, Yasuhiro

    2012-06-06

    Self-assembly of copper sulfate and a poly(imidazole-acrylamide) amphiphile provided a highly active, reusable, globular, solid-phase catalyst for click chemistry. The self-assembled polymeric Cu catalyst was readily prepared from poly(N-isopropylacrylamide-co-N-vinylimidazole) and CuSO(4) via coordinative convolution. The surface of the catalyst was covered with globular particles tens of nanometers in diameter, and those sheetlike composites were layered to build an aggregated structure. Moreover, the imidazole units in the polymeric ligand coordinate to CuSO(4) to give a self-assembled, layered, polymeric copper complex. The insoluble amphiphilic polymeric imidazole Cu catalyst with even 4.5-45 mol ppm drove the Huisgen 1,3-dipolar cycloaddition of a variety of alkynes and organic azides, including the three-component cyclization of a variety of alkynes, organic halides, and sodium azide. The catalytic turnover number and frequency were up to 209000 and 6740 h(-1), respectively. The catalyst was readily reused without loss of catalytic activity to give the corresponding triazoles quantitatively.

  6. Removal of volatile organic compounds using amphiphilic cyclodextrin-coated polypropylene

    Directory of Open Access Journals (Sweden)

    Ludmilla Lumholdt

    2014-11-01

    Full Text Available Polypropylene nonwovens were functionalised using a self-assembled, amphiphilic cyclodextrin coating and the potential for water purification by removal of pollutants was studied. As benzene is one of the problematic compounds in the Water Framework Directive, six volatile organic compounds (benzene and five benzene-based substances were chosen as model compounds. The compounds were tested as a mixture in order to provide a more realistic situation since the wastewater will be a complex mixture containing multiple pollutants. The volatile organic compounds are known to form stable inclusion complexes with cyclodextrins. Six different amphiphilic cyclodextrin derivatives were synthesised in order to elucidate whether or not the uptake abilities of the coating depend on the structure of the derivative. Headspace gas chromatography was used for quantification of the uptake exploiting the volatile nature of benzene and its derivatives. The capacity was shown to increase beyond the expected stoichiometries of guest–host complexes with ratios of up to 16:1.

  7. Tumor penetrating peptides

    Directory of Open Access Journals (Sweden)

    Tambet eTeesalu

    2013-08-01

    Full Text Available Tumor-homing peptides can be used to deliver drugs into tumors. Phage library screening in live mice has recently identified homing peptides that specifically recognize the endothelium of tumor vessels, extravasate, and penetrate deep into the extravascular tumor tissue. The prototypic peptide of this class, iRGD (CRGDKGPDC, contains the integrin-binding RGD motif. RGD mediates tumor homing through binding to αv integrins, which are selectively expressed on various cells in tumors, including tumor endothelial cells. The tumor-penetrating properties of iRGD are mediated by a second sequence motif, R/KXXR/K. This C-end Rule (or CendR motif is active only when the second basic residue is exposed at the C-terminus of the peptide. Proteolytic processing of iRGD in tumors activates the cryptic CendR motif, which then binds to neuropilin-1 activating an endocytic bulk transport pathway through tumor tissue. Phage screening has also yielded tumor-penetrating peptides that function like iRGD in activating the CendR pathway, but bind to a different primary receptor. Moreover, novel tumor-homing peptides can be constructed from tumor-homing motifs, CendR elements and protease cleavage sites. Pathologies other than tumors can be targeted with tissue-penetrating peptides, and the primary receptor can also be a vascular zip code of a normal tissue. The CendR technology provides a solution to a major problem in tumor therapy, poor penetration of drugs into tumors. The tumor-penetrating peptides are capable of taking a payload deep into tumor tissue in mice, and they also penetrate into human tumors ex vivo. Targeting with these peptides specifically increases the accumulation in tumors of a variety of drugs and contrast agents, such as doxorubicin, antibodies and nanoparticle-based compounds. Remarkably the drug to be targeted does not have to be coupled to the peptide; the bulk transport system activated by the peptide sweeps along any compound that is

  8. Tumor-Penetrating Peptides

    Science.gov (United States)

    Teesalu, Tambet; Sugahara, Kazuki N.; Ruoslahti, Erkki

    2013-01-01

    Tumor-homing peptides can be used to deliver drugs into tumors. Phage library screening in live mice has recently identified homing peptides that specifically recognize the endothelium of tumor vessels, extravasate, and penetrate deep into the extravascular tumor tissue. The prototypic peptide of this class, iRGD (CRGDKGPDC), contains the integrin-binding RGD motif. RGD mediates tumor-homing through binding to αv integrins, which are selectively expressed on various cells in tumors, including tumor endothelial cells. The tumor-penetrating properties of iRGD are mediated by a second sequence motif, R/KXXR/K. This C-end Rule (or CendR) motif is active only when the second basic residue is exposed at the C-terminus of the peptide. Proteolytic processing of iRGD in tumors activates the cryptic CendR motif, which then binds to neuropilin-1 activating an endocytic bulk transport pathway through tumor tissue. Phage screening has also yielded tumor-penetrating peptides that function like iRGD in activating the CendR pathway, but bind to a different primary receptor. Moreover, novel tumor-homing peptides can be constructed from tumor-homing motifs, CendR elements and protease cleavage sites. Pathologies other than tumors can be targeted with tissue-penetrating peptides, and the primary receptor can also be a vascular “zip code” of a normal tissue. The CendR technology provides a solution to a major problem in tumor therapy, poor penetration of drugs into tumors. The tumor-penetrating peptides are capable of taking a payload deep into tumor tissue in mice, and they also penetrate into human tumors ex vivo. Targeting with these peptides specifically increases the accumulation in tumors of a variety of drugs and contrast agents, such as doxorubicin, antibodies, and nanoparticle-based compounds. Remarkably the drug to be targeted does not have to be coupled to the peptide; the bulk transport system activated by the peptide sweeps along any compound that is present in the

  9. Redistribution of Cholesterol in Model Lipid Membranes in Response to the Membrane-Active Peptide Alamethicin

    Science.gov (United States)

    Heller, William; Qian, Shuo

    2013-03-01

    The cellular membrane is a heterogeneous, dynamic mixture of molecules and macromolecules that self-assemble into a tightly-regulated functional unit that provides a semipermeable barrier between the cell and its environment. Among the many compositional differences between mammalian and bacterial cell membranes that impact its physical properties, one key difference is cholesterol content, which is more prevalent in mammals. Cholesterol is an amphiphile that associates with membranes and serves to maintain its fluidity and permeability. Membrane-active peptides, such as the alpha-helical peptide alamethicin, interact with membranes in a concentration- and composition-dependent manner to form transmembrane pores that are responsible for the lytic action of the peptide. Through the use of small-angle neutron scattering and deuterium labeling, it was possible to observe a redistribution of the lipid and cholesterol in unilamellar vesicles in response to the presence of alamethicin at a peptide-to-lipid ratio of 1/200. The results demonstrate that the membrane remodeling powers of alamethicin reach beyond the membrane thinning effect to altering the localization of specific components in the bilayer, complementing the accepted two-state mechanism of pore formation. Research was supported by U. S. DOE-OBER (CSMB; FWP ERKP291) and the U. S. DOE-BES Scientific User Facilities Division (ORNL's SNS and HFIR).

  10. Novel Endogenous Antimicrobial Peptides

    OpenAIRE

    Nordahl, Emma

    2009-01-01

    Antimicrobial peptides serve as a first line of defence against invading microorganisms and are an essential part of our fast innate immune system. They are ancient molecules found in all classes of life. Antimicrobial peptides rapidly kill a broad spectrum of microbes and are immunomodulatory, i.e. having additional actions influencing inflammation and other innate immune responses. Results presented in this thesis demonstrate that proteases of common human pathogens degrade and inactivate t...

  11. Short Stature

    DEFF Research Database (Denmark)

    Christesen, Henrik Boye Thybo; Pedersen, Birgitte Tønnes; Pournara, Effie

    2016-01-01

    The use of appropriate growth standards/references is of significant clinical importance in assessing the height of children with short stature as it may determine eligibility for appropriate therapy. The aim of this study was to determine the impact of using World Health Organization (WHO) instead...... of national growth standards/references on height assessment in short children. Data were collected from routine clinical practice (1998-2014) from nine European countries that have available national growth references and were enrolled in NordiNet® International Outcome Study (IOS) (NCT00960128), a large......-scale, non-interventional, multinational study. The patient cohort consisted of 5996 short pediatric patients diagnosed with growth hormone deficiency (GHD), Turner syndrome (TS) or born small for gestational age (SGA). The proportions of children with baseline height standard deviation score (SDS) below...

  12. Peptide aldehyde inhibitors of bacterial peptide deformylases.

    Science.gov (United States)

    Durand, D J; Gordon Green, B; O'Connell, J F; Grant, S K

    1999-07-15

    Bacterial peptide deformylases (PDF, EC 3.5.1.27) are metalloenzymes that cleave the N-formyl groups from N-blocked methionine polypeptides. Peptide aldehydes containing a methional or norleucinal inhibited recombinant peptide deformylase from gram-negative Escherichia coli and gram-positive Bacillus subtilis. The most potent inhibitor was calpeptin, N-CBZ-Leu-norleucinal, which was a competitive inhibitor of the zinc-containing metalloenzymes, E. coli and B. subtilis PDF with Ki values of 26.0 and 55.6 microM, respectively. Cobalt-substituted E. coli and B. subtilis deformylases were also inhibited by these aldehydes with Ki values for calpeptin of 9.5 and 12.4 microM, respectively. Distinct spectral changes were observed upon binding of calpeptin to the Co(II)-deformylases, consistent with the noncovalent binding of the inhibitor rather than the formation of a covalent complex. In contrast, the chelator 1,10-phenanthroline caused the time-dependent inhibition of B. subtilis Co(II)-PDF activity with the loss of the active site metal. The fact that calpeptin was nearly equipotent against deformylases from both gram-negative and gram-positive bacterial sources lends further support to the idea that a single deformylase inhibitor might have broad-spectrum antibacterial activity. Copyright 1999 Academic Press.

  13. Short communication

    African Journals Online (AJOL)

    Personal

    Short communication. A PRELIMINARY SURVEY OF ERYTHROCEBUS PATAS IN ANBESA CHAKA,. BAMBESI WOREDA OF BENISHANGUL-GUMUZ REGION, WESTERN ETHIOPIA. Solomon Yirga 1, Manyingerew Shenkut 1, .... the guard or watch dog of the group whereas the females are group leaders that initiate ...

  14. Short communication

    African Journals Online (AJOL)

    UPuser

    South African Society for Animal Science. 27. Short communication. Polymorphisms of the CAST gene in the Meishan and five other pig populations in China. Q.S. Wang. 1. , Y.C. Pan. 1#. , L.B. Sun. 2 and H. Meng. 1. 1 Department of Animal Science, School of Agriculture and Biology, Shanghai Jiaotong University, ...

  15. Short Report

    African Journals Online (AJOL)

    2016-10-02

    Oct 2, 2016 ... Short Report. Identifying educational strategies to assess and address the health needs of communities is a high priority, ... using different learning strategies and activities. One such setting is the community, as .... Using the IDEA framework in an interprofessional didactic elective course to facilitate positive ...

  16. Aggregation behavior or amphiphilic poly(2-alkyl-2-oxazoline) diblock copolymers in aqueous solution studied by fluorescence correlation spectroscopy

    Czech Academy of Sciences Publication Activity Database

    Bonné, T. B.; Lüdtke, K.; Jordan, R.; Štěpánek, Petr; Papadakis, C. M.

    2004-01-01

    Roč. 282, č. 12 (2004), s. 833-843 ISSN 0303-402X R&D Projects: GA AV ČR IAA4050403 Keywords : self-diffusion * fluorescence correlation spectroscopy * amphiphilic diblock copolymers Subject RIV: CD - Macromolecular Chemistry Impact factor: 1.110, year: 2004

  17. Triblock Copolymers with Grafted Fluorine-Free Amphiphilic Non-Ionic Side Chains for Antifouling and Fouling-Release Applications

    Energy Technology Data Exchange (ETDEWEB)

    Y Cho; H Sundaram; C Weinman; M Paik; M Dimitriou; J Finlay; M Callow; J Callow; E Kramer; C Ober

    2011-12-31

    Fluorine-free, amphiphilic, nonionic surface active block copolymers (SABCs) were synthesized through chemical modification of a polystyrene-block-poly(ethylene-ran-butylene)-block-polyisoprene triblock copolymer precursor with selected amphiphilic nonionic Brij and other surfactants. Amphiphilicity was imparted by a hydrophobic aliphatic group combined with a hydrophilic poly(ethylene glycol) (PEG) group-containing moiety. The surfaces were characterized by dynamic water contact angle, atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS), and near edge X-ray absorption fine structure (NEXAFS) analysis. In biofouling assays, settlement (attachment) of both spores of the green alga Ulva and cells of the diatom Navicula on SABCs modified with Brij nonionic side chains was significantly reduced relative to a PDMS standard, with a nonionic surfactant combining a PEG group and an aliphatic moiety demonstrating the best performance. Additionally, a fouling-release assay using sporelings (young plants) of Ulva and Navicula suggested that the SABC derived from nonionic Brij side chains also out-performed PDMS as a fouling-release material. Good antifouling and fouling-release properties were not demonstrated for the other two amphiphilic surfaces derived from silicone and aromatic group containing nonionic surfactants included in this study. The results suggest that small differences in chemical surface functionality impart more significant changes with respect to the antifouling settlement and fouling-release performance of materials than overall wettability behavior.

  18. Amphiphilic DNA tiles for controlled insertion and 2D assembly on fluid lipid membranes: the effect on mechanical properties.

    Science.gov (United States)

    Dohno, Chikara; Makishi, Shingo; Nakatani, Kazuhiko; Contera, Sonia

    2017-03-02

    Future lipid membrane-associated DNA nanostructures are expected to find applications ranging from synthetic biology to nanomedicine. Here we have designed and synthesized DNA tiles and modified them with amphiphilic covalent moieties. dod-DEG groups, which consist of a hydrophilic diethylene glycol (DEG) and a hydrophobic dodecyl group, are introduced at the phosphate backbone to create amphiphilic DNA strands which are subsequently introduced into one face of the DNA tiles. In this way the tile becomes able to stably bind to lipid membranes by insertion of the hydrophobic groups inside the bilayer core. The functionalized tiles do not aggregate in solution. Our results show that these amphiphilic DNA tiles can bind and assemble into 2D lattices on both gel and fluid lipid bilayers. The binding of the DNA structures to membranes is dependent on the lipid phase of the membrane, the concentration of Mg 2+ cations, the length of the amphiphilic modifications to the DNA as well as on the density of the modifications within the tile. Atomic force microscopy-based force spectroscopy is used to investigate the effect of the inserted DNA tiles on the mechanical properties of the lipid membranes. The results indicate that the insertion of DNA tiles produces an approx. 20% increase of the bilayer breakthrough force.

  19. Self-assembled structures of amphiphilic ionic block copolymers: Theory, self-consistent field modeling and experiment

    NARCIS (Netherlands)

    Borisov, O.V.; Zhulina, E.B.; Leermakers, F.A.M.; Muller, A.H.E.

    2011-01-01

    We present an overview of statistical thermodynamic theories that describe the self-assembly of amphiphilic ionic/hydrophobic diblock copolymers in dilute solution. Block copolymers with both strongly and weakly dissociating (pH-sensitive) ionic blocks are considered. We focus mostly on structural

  20. Adamantane-based amphiphiles (ADAs) for membrane protein study: importance of a detergent hydrophobic group in membrane protein solubilisation.

    Science.gov (United States)

    Chae, Pil Seok; Bae, Hyoung Eun; Das, Manabendra

    2014-10-21

    We prepared adamantane-containing amphiphiles and evaluated them using a large membrane protein complex in terms of protein solubilisation and stabilization efficacy. These agents were superior to conventional detergents, especially in terms of the membrane protein solubilisation efficiency, implying a new detergent structure-property relationship.

  1. Amphiphilic copolymers based on PEG-acrylate as surface active water viscosifiers : Towards new potential systems for enhanced oil recovery

    NARCIS (Netherlands)

    Raffa, Patrizio; Broekhuis, Antonius A.; Picchioni, Francesco

    2016-01-01

    With the purpose of investigating new potential candidates for enhanced oil recovery (EOR), amphiphilic copolymers based on Poly(ethylene glycol) methyl ether acrylate (PEGA) have been prepared by Atom Transfer Radical Polymerization (ATRP). A P(PEGA) homopolymer, a block copolymer with styrene

  2. Preparation and structural characterisation of novel and versatile amphiphilic octenyl succinic anhydride-modified hyaluronic acid derivatives

    DEFF Research Database (Denmark)

    Eenschooten, Corinne Diane; Guillaumie, Fanny; Kontogeorgis, Georgios

    2010-01-01

    The purpose of the present study was to prepare amphiphilic hyaluronic acid (HA) derivatives and to study the influence of a selection of reaction parameters on the degree of substitution (DS) of the derivatives. Octenyl succinic anhydride (OSA)–modified HA (OSA–HA) derivatives were prepared...

  3. Amphiphilic hollow porous shell encapsulated Au@Pd bimetal nanoparticles for aerobic oxidation of alcohols in water

    KAUST Repository

    Zou, Houbing

    2015-01-01

    © The Royal Society of Chemistry 2015. This work describes the design, synthesis and analysis of an amphiphilic hollow mesoporous shell encapsulating catalytically active Au@Pd bimetal nanoparticles. The particles exhibited excellent catalytic activity and stability in the aerobic oxidation of primary and secondary alcohols to their corresponding aldehydes or ketones in water when using air as an oxidizing agent under atmospheric pressure.

  4. Granin-derived peptides.

    Science.gov (United States)

    Troger, Josef; Theurl, Markus; Kirchmair, Rudolf; Pasqua, Teresa; Tota, Bruno; Angelone, Tommaso; Cerra, Maria C; Nowosielski, Yvonne; Mätzler, Raphaela; Troger, Jasmin; Gayen, Jaur R; Trudeau, Vance; Corti, Angelo; Helle, Karen B

    2017-07-01

    The granin family comprises altogether 7 different proteins originating from the diffuse neuroendocrine system and elements of the central and peripheral nervous systems. The family is dominated by three uniquely acidic members, namely chromogranin A (CgA), chromogranin B (CgB) and secretogranin II (SgII). Since the late 1980s it has become evident that these proteins are proteolytically processed, intragranularly and/or extracellularly into a range of biologically active peptides; a number of them with regulatory properties of physiological and/or pathophysiological significance. The aim of this comprehensive overview is to provide an up-to-date insight into the distribution and properties of the well established granin-derived peptides and their putative roles in homeostatic regulations. Hence, focus is directed to peptides derived from the three main granins, e.g. to the chromogranin A derived vasostatins, betagranins, pancreastatin and catestatins, the chromogranin B-derived secretolytin and the secretogranin II-derived secretoneurin (SN). In addition, the distribution and properties of the chromogranin A-derived peptides prochromacin, chromofungin, WE14, parastatin, GE-25 and serpinins, the CgB-peptide PE-11 and the SgII-peptides EM66 and manserin will also be commented on. Finally, the opposing effects of the CgA-derived vasostatin-I and catestatin and the SgII-derived peptide SN on the integrity of the vasculature, myocardial contractility, angiogenesis in wound healing, inflammatory conditions and tumors will be discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Peptide Optical waveguides.

    Science.gov (United States)

    Handelman, Amir; Apter, Boris; Shostak, Tamar; Rosenman, Gil

    2017-02-01

    Small-scale optical devices, designed and fabricated onto one dielectric substrate, create integrated optical chip like their microelectronic analogues. These photonic circuits, based on diverse physical phenomena such as light-matter interaction, propagation of electromagnetic waves in a thin dielectric material, nonlinear and electro-optical effects, allow transmission, distribution, modulation, and processing of optical signals in optical communication systems, chemical and biological sensors, and more. The key component of these optical circuits providing both optical processing and photonic interconnections is light waveguides. Optical confinement and transmitting of the optical waves inside the waveguide material are possible due to the higher refractive index of the waveguides in comparison with their surroundings. In this work, we propose a novel field of bionanophotonics based on a new concept of optical waveguiding in synthetic elongated peptide nanostructures composed of ordered peptide dipole biomolecules. New technology of controllable deposition of peptide optical waveguiding structures by nanofountain pen technique is developed. Experimental studies of refractive index, optical transparency, and linear and nonlinear waveguiding in out-of-plane and in-plane diphenylalanine peptide nanotubes have been conducted. Optical waveguiding phenomena in peptide structures are simulated by the finite difference time domain method. The advantages of this new class of bio-optical waveguides are high refractive index contrast, wide spectral range of optical transparency, large optical nonlinearity, and electro-optical effect, making them promising for new applications in integrated multifunctional photonic circuits. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.

  6. Diversity-oriented peptide stapling

    DEFF Research Database (Denmark)

    Tran, Thu Phuong; Larsen, Christian Ørnbøl; Røndbjerg, Tobias

    2017-01-01

    The introduction of macrocyclic constraints in peptides (peptide stapling) is an important tool within peptide medicinal chemistry for stabilising and pre-organising peptides in a desired conformation. In recent years, the copper-catalysed azide-alkyne cycloaddition (CuAAC) has emerged as a power......The introduction of macrocyclic constraints in peptides (peptide stapling) is an important tool within peptide medicinal chemistry for stabilising and pre-organising peptides in a desired conformation. In recent years, the copper-catalysed azide-alkyne cycloaddition (CuAAC) has emerged...... incorporating two azide-modified amino acids with 1,3,5-triethynylbenzene efficiently provides (i, i+7)- and (i, i+9)-stapled peptides with a single free alkyne positioned on the staple, that can be further conjugated or dimerised. A unique feature of the present method is that it provides easy access...

  7. Amphiphilic triblock copolymers with PEGylated hydrocarbon structures as environmentally friendly marine antifouling and fouling-release coatings.

    Science.gov (United States)

    Zhou, Zhaoli; Calabrese, David R; Taylor, Warren; Finlay, John A; Callow, Maureen E; Callow, James A; Fischer, Daniel; Kramer, Edward J; Ober, Christopher K

    2014-01-01

    The ideal marine antifouling (AF)/fouling-release (FR) coating should be non-toxic, while effectively either resisting the attachment of marine organisms (AF) or significantly reducing their strength of attachment (FR). Many recent studies have shown that amphiphilic polymeric materials provide a promising solution to producing such coatings due to their surface dual functionality. In this work, poly(ethylene glycol) (PEG) of different molecular weights (Mw = 350, 550) was coupled to a saturated difunctional alkyl alcohol to generate amphiphilic surfactants (PEG-hydrocarbon-OH). The resulting macromolecules were then used as side chains to covalently modify a pre-synthesized PS8 K-b-P(E/B)25 K-b-PI10 K (SEBI or K3) triblock copolymer, and the final polymers were applied to glass substrata through an established multilayer surface coating technique to prepare fouling resistant coatings. The coated surfaces were characterized with AFM, XPS and NEXAFS, and evaluated in laboratory assays with two important fouling algae, Ulva linza (a green macroalga) and Navicula incerta, a biofilm-forming diatom. The results suggest that these polymer-coated surfaces undergo surface reconstruction upon changing the contact medium (polymer/air vs polymer/water), due to the preferential interfacial aggregation of the PEG segment on the surface in water. The amphiphilic polymer-coated surfaces showed promising results as both AF and FR coatings. The sample with longer PEG chain lengths (Mw = 550 g mol(-1)) exhibited excellent properties against both algae, highlighting the importance of the chemical structures on ultimate biological performance. Besides reporting synthesis and characterization of this new type of amphiphilic surface material, this work also provides insight into the nature of PEG/hydrocarbon amphiphilic coatings, and this understanding may help in the design of future generations of fluorine-free, environmentally friendly AF/FR polymeric coatings.

  8. A Water-Soluble Cyclotriveratrylene-Based Supra-amphiphile: Synthesis, pH-Responsive Self-Assembly in Water, and Its Application in Controlled Drug Release.

    Science.gov (United States)

    Xia, Danyu; Li, Yang; Jie, Kecheng; Shi, Bingbing; Yao, Yong

    2016-06-17

    A new water-soluble cyclotriveratrylene (WCTV) was designed and synthesized, and benzyldimethyldodecylammonium chloride (G) was chosen as the guest molecule to construct a supra-amphiphile by the host-guest interaction between WCTV and G in water, which is pH responsive. The supra-amphiphiles self-assembled into vesicles in water. When the pH of the solution was below 7.0, the supra-amphiphile disassociated, and the vesicles collapsed. Then, the pH-responsive self-assembly system was utilized for controlled drug release.

  9. Sugar-based amphiphilic polymers for biomedical applications: from nanocarriers to therapeutics.

    Science.gov (United States)

    Gu, Li; Faig, Allison; Abdelhamid, Dalia; Uhrich, Kathryn

    2014-10-21

    Various therapeutics exhibit unfavorable physicochemical properties or stability issues that reduce their in vivo efficacy. Therefore, carriers able to overcome such challenges and deliver therapeutics to specific in vivo target sites are critically needed. For instance, anticancer drugs are hydrophobic and require carriers to solubilize them in aqueous environments, and gene-based therapies (e.g., siRNA or pDNA) require carriers to protect the anionic genes from enzymatic degradation during systemic circulation. Polymeric micelles, which are self-assemblies of amphiphilic polymers (APs), constitute one delivery vehicle class that has been investigated for many biomedical applications. Having a hydrophobic core and a hydrophilic shell, polymeric micelles have been used as drug carriers. While traditional APs are typically comprised of nondegradable block copolymers, sugar-based amphiphilic polymers (SBAPs) synthesized by us are comprised of branched, sugar-based hydrophobic segments and a hydrophilic poly(ethylene glycol) chain. Similar to many amphiphilic polymers, SBAPs self-assemble into polymeric micelles. These nanoscale micelles have extremely low critical micelle concentrations offering stability against dilution, which occurs with systemic administration. In this Account, we illustrate applications of SBAPs for anticancer drug delivery via physical encapsulation within SBAP micelles and chemical conjugation to form SBAP prodrugs capable of micellization. Additionally, we show that SBAPs are excellent at stabilizing liposomal delivery systems. These SBAP-lipid complexes were developed to deliver hydrophobic anticancer therapeutics, achieving preferential uptake in cancer cells over normal cells. Furthermore, these complexes can be designed to electrostatically complex with gene therapies capable of transfection. Aside from serving as a nanocarrier, SBAPs have also demonstrated unique bioactivity in managing atherosclerosis, a major cause of cardiovascular

  10. Hydrophobic cotton textile surfaces using an amphiphilic graphene oxide (GO) coating

    International Nuclear Information System (INIS)

    Tissera, Nadeeka D.; Wijesena, Ruchira N.; Perera, J. Rangana; Nalin de Silva, K.M.; Amaratunge, Gehan A.J.

    2015-01-01

    Graphical abstract: - Highlights: • Different GO dispersions were prepared by sonicating different amounts of GO in water. Degree of exfoliation of these GO sheets in water was analyzed using Atomic Force Microscopy (AFM). • AFM results obtained showed higher the GO concentration on water more the size of GO sheets and lesser the degree of exfoliation. • GO with different amounts was deposited on cotton fabric using simple dyeing method. • High GO loading on cotton increase the surface area coverage of the textile fibers with GO sheets. This led to less edge to mid area ratio of grafted GO sheets. • As contribution of mid area of GO increase on fiber surface cotton fabric becomes more hydrophobic. • Amphiphilic property of GO sheets was used to lower the surface energy of the cotton fibers leading to hydrophobic property. - Abstract: We report for the first time hydrophobic properties on cotton fabric successfully achieved by grafting graphene oxide on the fabric surface, using a dyeing method. Graphite oxide synthesized by oxidizing natural flake graphite employing improved Hummer's method showed an inter layer spacing of ∼1 nm from XRD. Synthesized graphite oxide was exfoliated in water using ultrasound energy to obtain graphene oxide (GO). AFM data obtained for the graphene oxide dispersed in an aqueous medium revealed a non-uniform size distribution. FTIR characterization of the synthesized GO sheets showed both hydrophilic and hydrophobic functional groups present on the nano sheets giving them an amphiphilic property. GO flakes of different sizes were successfully grafted on to a cotton fabric surface using a dip dry method. Loading different amounts of graphene oxide on the cotton fiber surface allowed the fabric to demonstrate different degrees of hydrophobicity. The highest observed water contact angle was at 143° with the highest loading of graphene oxide. The fabric surfaces grafted with GO also exhibits adhesive type hydrophobicity

  11. Pronase E-Based Generation of Fluorescent Peptide Fragments: Tracking Intracellular Peptide Fate in Single Cells.

    Science.gov (United States)

    Mainz, Emilie R; Dobes, Nicholas C; Allbritton, Nancy L

    2015-08-04

    The ability to track intracellular peptide proteolysis at the single cell level is of growing interest, particularly as short peptide sequences continue to play important roles as biosensors, therapeutics, and endogenous participants in antigen processing and intracellular signaling. We describe a rapid and inexpensive methodology to generate fluorescent peptide fragments from a parent sequence with diverse chemical properties, including aliphatic, nonpolar, basic, acidic, and non-native amino acids. Four peptide sequences with existing biochemical applications were fragmented using incubation with Pronase E and/or formic acid, and in each case a complete set of fluorescent fragments was generated for use as proteolysis standards in chemical cytometry. Fragment formation and identity was monitored with capillary electrophoresis with laser-induced fluorescence detection (CE-LIF) and matrix assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-MS) to confirm the presence of all sequences and yield fragmentation profiles across Pronase E concentrations which can readily be used by others. As a pilot study, Pronase E-generated standards from an Abl kinase sensor and an ovalbumin antigenic peptide were then employed to identify proteolysis products arising from the metabolism of these sequences in single cells. The Abl kinase sensor fragmented at 4.2 ± 4.8 zmol μM(-1) s(-1) and the majority of cells possessed similar fragment identities. In contrast, an ovalbumin epitope peptide was degraded at 8.9 ± 0.1 zmol μM(-1) s(-1), but with differential fragment formation between individual cells. Overall, Pronase E-generated peptide standards were a rapid and efficient method to identify proteolysis products from cells.

  12. Peptide Integrated Optics.

    Science.gov (United States)

    Handelman, Amir; Lapshina, Nadezda; Apter, Boris; Rosenman, Gil

    2018-02-01

    Bio-nanophotonics is a wide field in which advanced optical materials, biomedicine, fundamental optics, and nanotechnology are combined and result in the development of biomedical optical chips. Silk fibers or synthetic bioabsorbable polymers are the main light-guiding components. In this work, an advanced concept of integrated bio-optics is proposed, which is based on bioinspired peptide optical materials exhibiting wide optical transparency, nonlinear and electrooptical properties, and effective passive and active waveguiding. Developed new technology combining bottom-up controlled deposition of peptide planar wafers of a large area and top-down focus ion beam lithography provides direct fabrication of peptide optical integrated circuits. Finding a deep modification of peptide optical properties by reconformation of biological secondary structure from native phase to β-sheet architecture is followed by the appearance of visible fluorescence and unexpected transition from a native passive optical waveguiding to an active one. Original biocompatibility, switchable regimes of waveguiding, and multifunctional nonlinear optical properties make these new peptide planar optical materials attractive for application in emerging technology of lab-on-biochips, combining biomedical photonic and electronic circuits toward medical diagnosis, light-activated therapy, and health monitoring. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Mechanism of membrane permeation induced by synthetic β-hairpin peptides.

    Science.gov (United States)

    Gupta, Kshitij; Jang, Hyunbum; Harlen, Kevin; Puri, Anu; Nussinov, Ruth; Schneider, Joel P; Blumenthal, Robert

    2013-11-05

    We have investigated the membrane destabilizing properties of synthetic amphiphilic cationic peptides, MAX1 and MAX35, which have the propensity to form β-hairpin structures under certain conditions, and a control non-β-hairpin-forming peptide MAX8V16E. All three peptides bind to liposomes containing a mixture of zwitterionic POPC and negatively charged POPS lipids as determined by Zeta potential measurements. Circular dichroism measurements indicated folding of MAX1 and MAX35 in the presence of the POPC/POPS liposomes, whereas no such folding was observed with MAX8V16E. There was no binding or folding of these peptides to liposomes containing only POPC. MAX1 and MAX35 induced release of contents from negatively charged liposomes, whereas MAX8V16E failed to promote solute release under identical conditions. Thus, MAX1 and MAX35 bind to, and fold at the surface of negatively charged liposomes adopting a lytic conformation. We ruled out leaky fusion as a mechanism of release by including 2 mol % PEG-PE in the liposomes, which inhibits aggregation/fusion but not folding of MAX or MAX-induced leakage. Using a concentration-dependent quenching probe (calcein), we determined that MAX-induced leakage of liposome contents was an all-or-none process. At MAX1 concentrations, which cause release of ~50% of the liposomes that contain small (R(h) peptides are relatively more stable than MAX8V16E barrels in the bilayer, suggesting that barrels of this size are responsible for the peptides lytic action. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  14. Neural tissue engineering: Bioresponsive nanoscaffolds using engineered self-assembling peptides.

    Science.gov (United States)

    Koss, K M; Unsworth, L D

    2016-10-15

    Rescuing or repairing neural tissues is of utmost importance to the patient's quality of life after an injury. To remedy this, many novel biomaterials are being developed that are, ideally, non-invasive and directly facilitate neural wound healing. As such, this review surveys the recent approaches and applications of self-assembling peptides and peptide amphiphiles, for building multi-faceted nanoscaffolds for direct application to neural injury. Specifically, methods enabling cellular interactions with the nanoscaffold and controlling the release of bioactive molecules from the nanoscaffold for the express purpose of directing endogenous cells in damaged or diseased neural tissues is presented. An extensive overview of recently derived self-assembling peptide-based materials and their use as neural nanoscaffolds is presented. In addition, an overview of potential bioactive peptides and ligands that could be used to direct behaviour of endogenous cells are categorized with their biological effects. Finally, a number of neurotrophic and anti-inflammatory drugs are described and discussed. Smaller therapeutic molecules are emphasized, as they are thought to be able to have less potential effect on the overall peptide self-assembly mechanism. Options for potential nanoscaffolds and drug delivery systems are suggested. Self-assembling nanoscaffolds have many inherent properties making them amenable to tissue engineering applications: ease of synthesis, ease of customization with bioactive moieties, and amenable for in situ nanoscaffold formation. The combination of the existing knowledge on bioactive motifs for neural engineering and the self-assembling propensity of peptides is discussed in specific reference to neural tissue engineering. Copyright © 2016. Published by Elsevier Ltd.

  15. A review of solute encapsulating nanoparticles used as delivery systems with emphasis on branched amphipathic peptide capsules.

    Science.gov (United States)

    Barros, Sheila M; Whitaker, Susan K; Sukthankar, Pinakin; Avila, L Adriana; Gudlur, Sushanth; Warner, Matt; Beltrão, Eduardo I C; Tomich, John M

    2016-04-15

    Various strategies are being developed to improve delivery and increase the biological half-lives of pharmacological agents. To address these issues, drug delivery technologies rely on different nano-sized molecules including: lipid vesicles, viral capsids and nano-particles. Peptides are a constituent of many of these nanomaterials and overcome some limitations associated with lipid-based or viral delivery systems, such as tune-ability, stability, specificity, inflammation, and antigenicity. This review focuses on the evolution of bio-based drug delivery nanomaterials that self-assemble forming vesicles/capsules. While lipid vesicles are preeminent among the structures; peptide-based constructs are emerging, in particular peptide bilayer delimited capsules. The novel biomaterial-Branched Amphiphilic Peptide Capsules (BAPCs) display many desirable properties. These nano-spheres are comprised of two branched peptides-bis(FLIVI)-K-KKKK and bis(FLIVIGSII)-K-KKKK, designed to mimic diacyl-phosphoglycerides in molecular architecture. They undergo supramolecular self-assembly and form solvent-filled, bilayer delineated capsules with sizes ranging from 20 nm to 2 μm depending on annealing temperatures and time. They are able to encapsulate different fluorescent dyes, therapeutic drugs, radionuclides and even small proteins. While sharing many properties with lipid vesicles, the BAPCs are much more robust. They have been analyzed for stability, size, cellular uptake and localization, intra-cellular retention and, bio-distribution both in culture and in vivo. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Self-Assembled ROS-Sensitive Polymer-Peptide Therapeutics Incorporating Built-in Reporters for Evaluation of Treatment Efficacy.

    Science.gov (United States)

    Qiao, Zeng-Ying; Zhao, Wen-Jing; Cong, Yong; Zhang, Di; Hu, Zhiyuan; Duan, Zhong-Yu; Wang, Hao

    2016-05-09

    One of the major challenges in current cancer therapy is to maximize therapeutic effect and evaluate tumor progression under the scheduled treatment protocol. To address these challenges, we synthesized the cytotoxic peptide (KLAKLAK)2 (named KLAK) conjugated amphiphilic poly(β-thioester)s copolymers (H-P-K) composed of reactive oxygen species (ROS) sensitive backbones and hydrophilic polyethylene glycol (PEG) side chains. H-P-K could self-assemble into micelle-like nanoparticles by hydrophobic interaction with copolymer backbones as cores and PEG and KLAK as shells. The assembled polymer-peptide nanoparticles remarkably improved cellular internalization and accumulation of therapeutic KLAK in cells. Compared to free KLAK peptide, the antitumor activity of H-P-K was significantly enhanced up to ∼400 times, suggesting the effectiveness of the nanoscaled polymer-peptide conjugation as biopharmaceuticals. The higher antitumor activity of nanoparticles was attributed to the efficient disruption of mitochondrial membranes and subsequent excessive ROS production in cells. To realize the ROS monitoring and treatment evaluation, we encapsulated squaraine (SQ) dyes as built-in reporters in ROS-sensitive H-P-K micelles. The overgenerated ROS around mitochondria stimulated the swelling of nanoparticles and subsequent release of SQ, which formed H-aggregates and significantly increased the photoacoustic (PA) signal. We believed that this self-assembled polymer-peptide nanotherapeutics incorporating built-in reporters has great potential for high antitumor performance and in situ treatment evaluation.

  17. Fibrils from designed non-amyloid-related synthetic peptides induce AA-amyloidosis during inflammation in an animal model.

    Directory of Open Access Journals (Sweden)

    Per Westermark

    Full Text Available BACKGROUND: Mouse AA-amyloidosis is a transmissible disease by a prion-like mechanism where amyloid fibrils act by seeding. Synthetic peptides with no amyloid relationship can assemble into amyloid-like fibrils and these may have seeding capacity for amyloid proteins. PRINCIPAL FINDINGS: Several synthetic peptides, designed for nanotechnology, have been examined for their ability to produce fibrils with Congo red affinity and concomitant green birefringence, affinity for thioflavin S and to accelerate AA-amyloidosis in mice. It is shown that some amphiphilic fibril-forming peptides not only produced Congo red birefringence and showed affinity for thioflavin S, but they also shortened the lag phase for systemic AA-amyloidosis in mice when they were given intravenously at the time of inflammatory induction with silver nitride. Peptides, not forming amyloid-like fibrils, did not have such properties. CONCLUSIONS: These observations should caution researchers and those who work with synthetic peptides and their derivatives to be aware of the potential health concerns.

  18. The first peptides: The evolutionary transition between prebiotic amino acids and early proteins

    NARCIS (Netherlands)

    van der Gulik, P.; Massar, S.; Gilis, D.; Buhrman, H.; Rooman, M.

    2009-01-01

    The issues we attempt to tackle here are what the first peptides did look like when they emerged on the primitive earth, and what simple catalytic activities they fulfilled. We conjecture that the early functional peptides were short (3-8 amino acids long), were made of those amino acids, Gly, Ala,

  19. Novel human bioactive peptides identified in apolipoprotein B : evaluation of their therapeutic potential

    NARCIS (Netherlands)

    Gaglione, Rosa; Dell'Olmo, Eliana; Bosso, Andrea; Chino, Marco; Pane, Katia; Ascione, Flora; Itri, Francesco; Caserta, Sergio; Amoresano, Angela; Lombardi, Angelina; Haagsman, Henk P; Piccoli, Renata; Pizzo, Elio; Veldhuizen, Edwin J A; Notomista, Eugenio; Arciello, Angela

    2017-01-01

    Host defence peptides (HDPs) are short, cationic amphipathic peptides that play a key role in the response to infection and inflammation in all complex life forms. It is increasingly emerging that HDPs generally have a modest direct activity against a broad range of microorganisms, and that their

  20. Synthetic antibiofilm peptides.

    Science.gov (United States)

    de la Fuente-Núñez, César; Cardoso, Marlon Henrique; de Souza Cândido, Elizabete; Franco, Octavio Luiz; Hancock, Robert E W

    2016-05-01

    Bacteria predominantly exist as multicellular aggregates known as biofilms that are associated with at least two thirds of all infections and exhibit increased adaptive resistance to conventional antibiotic therapies. Therefore, biofilms are major contributors to the global health problem of antibiotic resistance, and novel approaches to counter them are urgently needed. Small molecules of the innate immune system called host defense peptides (HDPs) have emerged as promising templates for the design of potent, broad-spectrum antibiofilm agents. Here, we review recent developments in the new field of synthetic antibiofilm peptides, including mechanistic insights, synergistic interactions with available antibiotics, and their potential as novel antimicrobials against persistent infections caused by biofilms. This article is part of a Special Issue entitled: Antimicrobial peptides edited by Karl Lohner and Kai Hilpert. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Lipid nanocarriers (GeluPearl) containing amphiphilic lipid Gelucire 50/13 as a novel stabilizer: fabrication, characterization and evaluation for oral drug delivery

    Energy Technology Data Exchange (ETDEWEB)

    Date, Abhijit A; Nagarsenker, Mangal S [Department of Pharmaceutics, Bombay College of Pharmacy, Kalina, Santacruz (E.), Mumbai (India); Vador, Nimish; Jagtap, Aarti, E-mail: mangal_nag511@yahoo.co.in, E-mail: mangal@bcp.edu.in [Department of Pharmacology, Bombay College of Pharmacy, Kalina, Santacruz (E.), Mumbai (India)

    2011-07-08

    Purpose. To evaluate the ability of Gelucire 50/13 (an amphiphilic lipid excipient) to act as a stabilizer for lipid nanocarriers such as solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) and to establish the ability of Gelucire 50/13 based lipid nanocarriers to improve oral delivery of hydrophobic drugs using repaglinide (RPG) as a model drug. Methods. The ability of Gelucire 50/13 to nanosize various solid lipids was evaluated. The ability of Gelucire 50/13 to yield NLC was evaluated by using Precirol ATO 5 as a model solid lipid and various liquid lipids (oils). Gelucire 50/13 based NLC (GeluPearl) were evaluated for their ability to improve the efficacy of RPG on oral administration in comparison to RPG tablets. The short term stability of RPG-GeluPearl was evaluated at 25 deg. C/60% RH. Results. Gelucire 50/13 could successfully yield SLN and NLC of various solid lipids, demonstrating its potential to act as a novel stabilizer. DSC studies indicated that Gelucire 50/13 interacts with Precirol ATO 5 and this interaction suppresses polymorphic transitions of both the components. RPG-GeluPearl exhibited significantly higher anti-diabetic activity compared to marketed RPG tablets. RPG-GeluPearl demonstrated good colloidal and chemical stability at the end of 1 month.

  2. Lipid nanocarriers (GeluPearl) containing amphiphilic lipid Gelucire 50/13 as a novel stabilizer: fabrication, characterization and evaluation for oral drug delivery

    Science.gov (United States)

    Date, Abhijit A.; Vador, Nimish; Jagtap, Aarti; Nagarsenker, Mangal S.

    2011-07-01

    Purpose. To evaluate the ability of Gelucire 50/13 (an amphiphilic lipid excipient) to act as a stabilizer for lipid nanocarriers such as solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) and to establish the ability of Gelucire 50/13 based lipid nanocarriers to improve oral delivery of hydrophobic drugs using repaglinide (RPG) as a model drug. Methods. The ability of Gelucire 50/13 to nanosize various solid lipids was evaluated. The ability of Gelucire 50/13 to yield NLC was evaluated by using Precirol ATO 5 as a model solid lipid and various liquid lipids (oils). Gelucire 50/13 based NLC (GeluPearl) were evaluated for their ability to improve the efficacy of RPG on oral administration in comparison to RPG tablets. The short term stability of RPG-GeluPearl was evaluated at 25 °C/60% RH. Results. Gelucire 50/13 could successfully yield SLN and NLC of various solid lipids, demonstrating its potential to act as a novel stabilizer. DSC studies indicated that Gelucire 50/13 interacts with Precirol ATO 5 and this interaction suppresses polymorphic transitions of both the components. RPG-GeluPearl exhibited significantly higher anti-diabetic activity compared to marketed RPG tablets. RPG-GeluPearl demonstrated good colloidal and chemical stability at the end of 1 month. Indian patent application number 2167/MUM/2008.

  3. Lipid nanocarriers (GeluPearl) containing amphiphilic lipid Gelucire 50/13 as a novel stabilizer: fabrication, characterization and evaluation for oral drug delivery

    International Nuclear Information System (INIS)

    Date, Abhijit A; Nagarsenker, Mangal S; Vador, Nimish; Jagtap, Aarti

    2011-01-01

    Purpose. To evaluate the ability of Gelucire 50/13 (an amphiphilic lipid excipient) to act as a stabilizer for lipid nanocarriers such as solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) and to establish the ability of Gelucire 50/13 based lipid nanocarriers to improve oral delivery of hydrophobic drugs using repaglinide (RPG) as a model drug. Methods. The ability of Gelucire 50/13 to nanosize various solid lipids was evaluated. The ability of Gelucire 50/13 to yield NLC was evaluated by using Precirol ATO 5 as a model solid lipid and various liquid lipids (oils). Gelucire 50/13 based NLC (GeluPearl) were evaluated for their ability to improve the efficacy of RPG on oral administration in comparison to RPG tablets. The short term stability of RPG-GeluPearl was evaluated at 25 deg. C/60% RH. Results. Gelucire 50/13 could successfully yield SLN and NLC of various solid lipids, demonstrating its potential to act as a novel stabilizer. DSC studies indicated that Gelucire 50/13 interacts with Precirol ATO 5 and this interaction suppresses polymorphic transitions of both the components. RPG-GeluPearl exhibited significantly higher anti-diabetic activity compared to marketed RPG tablets. RPG-GeluPearl demonstrated good colloidal and chemical stability at the end of 1 month.

  4. Single-component solid lipid nanocarriers prepared with ultra-long chain amphiphilic lipids

    DEFF Research Database (Denmark)

    Wei, Wei; Lu, Xiaonan; Wang, Zegao

    2017-01-01

    HYPOTHESIS: Synthetic sugar alcohol mono-behenates with high melting points, surface activity and resistance to enzymatic lipolysis, are expected to form stable single-component solid lipid nanocarriers (SC-SLNs). The preparation methods and the polar head group of the molecules should affect...... the smallest mean size (∼100nm with PdI of 0.26). In addition, they displayed high entrapment efficiency of fenofibrate (95%) and long term drug release. Nanocarriers prepared by emulsification-diffusion method entrapped fenofibrate into lipid bilayers. In contrast, Nanocarriers prepared by melting......-probe sonication method had a micelle structure with fenofibrate incorporated into a lipid monolayer. This study provides an insight into the systematic development of novel amphiphilic lipids for solid lipid-based drug delivery system....

  5. pH-Sensitive Amphiphilic Block-Copolymers for Transport and Controlled Release of Oxygen

    KAUST Repository

    Patil, Yogesh Raghunath

    2017-05-31

    Saturated fluorocarbons, their derivatives and emulsions are capable of dissolving anomalously high amounts of oxygen and other gases. The mechanistic aspects of this remarkable effect remain to be explored experimentally. Here, the synthesis of a library of amphiphilic fluorous block-copolymers incorporating different fluorinated monomers is described, and the capacity of these copolymers for oxygen transport in water is systematically investigated. The structure of the fluorous monomer employed was found to have a profound effect on both the oxygen-carrying capacity and the gas release kinetics of the polymer emulsions. Furthermore, the release of O2 from the polymer dispersions could be triggered by changing the pH of the solution. This is the first example of a polymer-based system for controlled release of a non-polar, non-covalently entrapped respiratory gas.

  6. Self-assembly of block copolymer-based ionic supramolecules based upon multi-tail amphiphiles

    DEFF Research Database (Denmark)

    Asad Ayoubi, M.; Almdal, Kristoffer; Zhu, K.

    2015-01-01

    Utilising simple acid-base titration chemistry, a new family of Linear-b-Amphiphilic Comb (L-b-AC) ionic supramolecules [Soft Matter 2013, 9, 1540-1555] featuring multi-tail side-chains have been synthesized and examined by synchrotron SAXS. To three different parent diblock copolymers of poly......(styrene)-b-poly(methacrylic acid) PS-b-PMAA multi-tail ammonium side-chains of (C8)2-, (C8)4- or (C12)2-type were attached at various side-chain grafting densities (X), making it possible to separate effects of the details of the AC-block architecture from effects of the overall volume fraction of the AC block. The micro...

  7. Supramolecular self-assembly of nonlinear amphiphilic and double hydrophilic block copolymers in aqueous solutions.

    Science.gov (United States)

    Ge, Zhishen; Liu, Shiyong

    2009-09-17

    Supramolecular self-assembly of block copolymers in aqueous solution has received ever-increasing interest over the past few decades due to diverse biological and technological applications in drug delivery, imaging, sensing and catalysis. In addition to relative block lengths, molecular weights and solution conditions, chain architectures of block copolymers can also dramatically affect their self-assembling properties in selective solvents. This feature article mainly focuses on recent developments in the field of supramolecular self-assembly of amphiphilic and double hydrophilic block copolymers (DHBCs) possessing nonlinear chain topologies, including miktoarm star polymers, dendritic-linear block copolymers, cyclic block copolymers and comb-shaped copolymer brushes. Copyright © 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Biphasic catalysis using amphiphilic polyphenols-chelated noble metals as highly active and selective catalysts

    Science.gov (United States)

    Mao, Hui; Yu, Hong; Chen, Jing; Liao, Xuepin

    2013-01-01

    In the field of catalysis, it is highly desired to develop novel catalysts that combine the advantages of both homogeneous and heterogeneous catalysts. Here we disclose that the use of plant pholyphenol as amphiphilic large molecule ligand/stabilizer allows for the preparation of noble metal complex and noble metal nanoparticle catalysts. These catalysts are found to be highly selective and active in aqueous-organic biphasic catalysis of cinnamaldehyde and quinoline, and can be reused at least 3 times without significant loss of activity. Moreover, the catalytic activity and reusability of the catalysts can be rationally controlled by simply adjusting the content of polyphenols in the catalysts. Our strategy may be extended to design a wide range of aqueous-organic biphasic catalysis system. PMID:23863916

  9. Biphasic catalysis using amphiphilic polyphenols-chelated noble metals as highly active and selective catalysts.

    Science.gov (United States)

    Mao, Hui; Yu, Hong; Chen, Jing; Liao, Xuepin

    2013-01-01

    In the field of catalysis, it is highly desired to develop novel catalysts that combine the advantages of both homogeneous and heterogeneous catalysts. Here we disclose that the use of plant polyphenol as amphiphilic large molecule ligand/stabilizer allows for the preparation of noble metal complex and noble metal nanoparticle catalysts. These catalysts are found to be highly selective and active in aqueous-organic biphasic catalysis of cinnamaldehyde and quinoline, and can be reused at least 3 times without significant loss of activity. Moreover, the catalytic activity and reusability of the catalysts can be rationally controlled by simply adjusting the content of polyphenols in the catalysts. Our strategy may be extended to design a wide range of aqueous-organic biphasic catalysis system.

  10. Salt Effect on the Cloud Point Phenomenon of Amphiphilic Drug-Hydroxypropylmethyl Cellulose System

    Directory of Open Access Journals (Sweden)

    Mohd. Sajid Ali

    2014-01-01

    Full Text Available Effect of two amphiphilic drugs (tricyclic antidepressant, nortriptyline hydrochloride (NORT, and nonsteroidal anti-inflammatory drug, sodium salt of ibuprofen (IBF on the cloud point of biopolymer hydroxypropylmethyl cellulose (HPMC was studied. Effect of NaCl was also seen on the CP of HPMC-drug system. CP of HPMC increases uniformly on increasing the (drug. Both drugs, though one being anionic (IBF and other cationic (NORT, affect the CP in almost the same manner but with different extent implying the role of hydrophobicity in the interaction between drug and polymer. Salt affects the CP of the drug in a dramatic way as low concentration of salt was only able to increase the value of the CP, though not affecting the pattern. However, in presence of high concentration of salts, minimum was observed on CP versus (drug plots. Various thermodynamic parameters were evaluated and discussed on the basis of the observed results.

  11. Structure-property relationship in cytotoxicity and cell uptake of poly(2-oxazoline) amphiphiles

    KAUST Repository

    Luxenhofer, Robert

    2011-07-01

    The family of poly(2-oxazoline)s (POx) is being increasingly investigated in the context of biomedical applications. We tested the relative cytotoxicity of POx and were able to confirm that these polymers are typically not cytotoxic even at high concentrations. Furthermore, we report structure-uptake relationships of a series of amphiphilic POx block copolymers that have different architectures, molar mass and chain termini. The rate of endocytosis can be fine-tuned over a broad range by changing the polymer structure. The cellular uptake increases with the hydrophobic character of the polymers and is observed even at nanomolar concentrations. Considering the structural versatility of this class of polymers, the relative ease of preparation and their stability underlines the potential of POx as a promising platform candidate for the preparation of next-generation polymer therapeutics.

  12. Synthesis, Amphiphilic Property and Thermal Stability of Novel Main-chain Poly(o-carborane-benzoxazines)

    Science.gov (United States)

    Yang, Xiaoxue; Han, Guo; Yang, Zhen; Zhang, Xiaoa; Jiang, Shengling; Lyu, Yafei

    2017-10-01

    Five poly(o-carborane-benzoxazines) were synthesized via Mannich reaction of o-carborane bisphenol, paraformaldehyde, and diamine, and their structures were well characterized. Light transmission and 1H NMR in D2O confirmed that poly(o-carborane-benzoxazines) with PEG segments showed excellent water solubility and amphiphilic property. TGA analyses were conducted under nitrogen and air, and the results showed that the polymers own high initial decomposition temperatures owing to the shielding effect of carborane moiety on its adjacent aromatic structures. Besides, poly(o-carborane-benzoxazines) own high char yield at elevated temperatures, for the boron atom could combine with oxygen from the polymer structure or/and the air and be oxidized to form boron oxide, and thus the polymer weight is retained to a large extent. PEG segments had an adverse effect on the initial decomposition and char yield, and thus their concentration should be adjusted to control the polymer’s thermal stability.

  13. Novel fluorescent amphiphilic block copolymers: photophysics behavior and interactions with DNA

    Directory of Open Access Journals (Sweden)

    2007-06-01

    Full Text Available In this study, novel amphiphilic fluorescent copolymers poly(N-vinylpyrrolidone-b-poly(N-methacryloyl-N'-(α-naphthylthiourea (PVP-b-PNT were synthesized via ATRP with poly(N-vinylpyrrolidone-Cl as macroinitiator and N-methacryloyl-N'-α-naphthylthiourea (NT as hydrophobic segment. PVP-b-PNT copolymers were characterized by 1H NMR, GPC-MALLS and fluorescence measurements. The aggregation behavior of PVP-b-PNT in water was investigated by transmission electron microscope (TEM and dynamic light scattering (DLS measurement. The photophysics behavior of PVP-b-PNT showed that block copolymer formed strong excimer. The interaction of DNA with the block copolymer made the excimer of block copolymer quench. The cytotoxicity result of PVP-b-PNT in cell culture in vitro indicated that this copolymer PVP-b-PNT had good biocompatibility.

  14. Linear-g-hyperbranched and cyclodextrin-based amphiphilic block copolymer as a multifunctional nanocarrier

    Directory of Open Access Journals (Sweden)

    Yamei Zhao

    2014-11-01

    Full Text Available In this paper, a novel, multifunctional polymer nanocarrier was designed to provide adequate volume for high drug loading, to afford a multiregion encapsulation ability, and to achieve controlled drug release. An amphiphilic, triblock polymer (ABC with hyperbranched polycarbonsilane (HBPCSi and β-cyclodextrin (β-CD moieties were first synthesized by the combination of a two-step reversible addition-fragmentation transfer polymerization into a pseudo-one-step hydrosilylation and quaternization reaction. The ABC then self-assembled into stable micelles with a core–shell structure in aqueous solution. These resulting micelles are multifunctional nanocarriers which possess higher drug loading capability due to the introduction of HBPCSi segments and β-CD moieties, and exhibit controlled drug release based on the diffusion release mechanism. The novel multifunctional nanocarrier may be applicable to produce highly efficient and specialized delivery systems for drugs, genes, and diagnostic agents.

  15. Self assembly of amphiphilic C60 fullerene derivatives into nanoscale supramolecular structures

    Directory of Open Access Journals (Sweden)

    Casscells S Ward

    2007-08-01

    Full Text Available Abstract Background The amphiphilic fullerene monomer (AF-1 consists of a "buckyball" cage to which a Newkome-like dendrimer unit and five lipophilic C12 chains positioned octahedrally to the dendrimer unit are attached. In this study, we report a novel fullerene-based liposome termed 'buckysome' that is water soluble and forms stable spherical nanometer sized vesicles. Cryogenic electron microscopy (Cryo-EM, transmission electron microscopy (TEM, and dynamic light scattering (DLS studies were used to characterize the different supra-molecular structures readily formed from the fullerene monomers under varying pH, aqueous solvents, and preparative conditions. Results Electron microscopy results indicate the formation of bilayer membranes with a width of ~6.5 nm, consistent with previously reported molecular dynamics simulations. Cryo-EM indicates the formation of large (400 nm diameter multilamellar, liposome-like vesicles and unilamellar vesicles in the size range of 50–150 nm diameter. In addition, complex networks of cylindrical, tube-like aggregates with varying lengths and packing densities were observed. Under controlled experimental conditions, high concentrations of spherical vesicles could be formed. In vitro results suggest that these supra-molecular structures impose little to no toxicity. Cytotoxicity of 10–200 μM buckysomes were assessed in various cell lines. Ongoing studies are aimed at understanding cellular internalization of these nanoparticle aggregates. Conclusion In this current study, we have designed a core platform based on a novel amphiphilic fullerene nanostructure, which readily assembles into supra-molecular structures. This delivery vector might provide promising features such as ease of preparation, long-term stability and controlled release.

  16. In vitro evaluation of anticancer nanomedicines based on doxorubicin and amphiphilic Y-shaped copolymers

    Directory of Open Access Journals (Sweden)

    Li D

    2012-05-01

    Full Text Available Di Li,1,2,* Jian Xun Ding,1,3,* Zhao Hui Tang,1 Hai Sun,1 Xiu Li Zhuang,1 Jing Zhe Xu,2 Xue Si Chen1 1Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 2Department of Chemistry, Yanbian University, Yanji, 3Graduate University of Chinese Academy of Sciences, Beijing, China *These authors contributed equally to this workAbstract: Four monomethoxy poly(ethylene glycol-poly(L-lactide-co-glycolide2 (mPEG-P(LA-co-GA2 copolymers were synthesized by ring-opening polymerization of L-lactide and glycolide with double hydroxyl functionalized mPEG (mPEG-(OH2 as macroinitiator and stannous octoate as catalyst. The copolymers self-assembled into nanoscale micellar/vesicular aggregations in phosphate buffer at pH 7.4. Doxorubicin (DOX, an anthracycline anticancer drug, was loaded into the micellar/vesicular nanoparticles, yielding micellar/vesicular nanomedicines. The in vitro release behaviors could be adjusted by content of hydrophobic polyester and pH of the release medium. In vitro cell experiments showed that the intracellular DOX release could be adjusted by content of P(LA-co-GA, and the nanomedicines displayed effective proliferation inhibition against Henrietta Lacks’s cells with different culture times. Hemolysis tests indicated that the copolymers were hemocompatible, and the presence of copolymers could reduce the hemolysis ratio of DOX significantly. These results suggested that the novel anticancer nanomedicines based on DOX and amphiphilic Y-shaped copolymers were attractive candidates as tumor tissular and intracellular targeting drug delivery systems in vivo, with enhanced stability during circulation and accelerated drug release at the target sites.Keywords: amphiphilic Y-shaped copolymer, anticancer nanomedicine, cellular proliferation inhibition, doxorubicin

  17. Facile synthesis and characterization of novel biodegradable amphiphilic block copolymers bearing pendant hydroxyl groups

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Gaicen; Fan, Xiaoshan; Xu, Bingcan; Zhang, Delong; Hu, Zhiguo, E-mail: zghu@htu.cn

    2014-10-01

    Novel amphiphilic block copolymers bearing pendant hydroxyl groups polylactide-b–poly(3,3-bis(Hydroxymethyl–triazolylmethyl) oxetane)-b–polylactide (PLA-b–PHMTYO-b–PLA) were synthesized via a facile and efficient method. First, the block copolymer intermediates polylactide-b–poly(3,3-Diazidomethyloxetane)-b–polylactide (PLA-b–PBAMO-b–PLA) were synthesized through ring-opening polymerization of lactide using PBAMO as a macroinitiator. Following “Click” reaction of PLA-b–PBAMO-b–PLA with propargyl alcohol provided the targeted amphiphilic block copolymers PLA-b–PHMTYO-b–PLA with pendant hydroxyl groups. The composition and structure of prepared copolymers were characterized by {sup 1}H nuclear magnetic resonance ({sup 1}H NMR) spectroscopy, Fourier transform infrared (FT-IR) and gel permeation chromatography (GPC). The self-assembly behavior of the copolymers in water was investigated by transmission electron microscope (TEM), dynamic light scattering (DLS) and static light scattering (SLS). The results showed that the novel copolymers PLA-b–PHMTYO-b–PLA self-assembled into spherical micelles with diameters ranging from 100 nm to 200 nm in aqueous solution. These copolymers also exhibited low critical micellar concentrations (CMC: 6.9 × 10{sup −4} mg/mL and 3.9 × 10{sup −5} mg/mL, respectively). In addition, the in vitro cytotoxicity of these copolymers was determined in the presence of L929 cells. The results showed that the block copolymers PLA-b–PHMTYO-b–PLA exhibited better biocompatibility. Therefore, these well-defined copolymers are expected to find some applications in drug delivery or tissue engineering. - Highlights: • The method to synthesize PLA-b–PHMTYO-b–PLA is relatively facile and efficient. • PLA-b–PHMTYO-b–PLA self-assembles into spherical micelles with low CMC in water. • PLA-b–PHMTYO-b–PLA exhibits better biocompatibility and biodegradability.

  18. Nanotoxicity comparison of four amphiphilic polymeric micelles with similar hydrophilic or hydrophobic structure.

    Science.gov (United States)

    Zhao, Bo; Wang, Xue-Qing; Wang, Xiao-You; Zhang, Hua; Dai, Wen-Bing; Wang, Jun; Zhong, Zhen-Lin; Wu, Hou-Nan; Zhang, Qiang

    2013-10-03

    Nanocarriers represent an attractive means of drug delivery, but their biosafety must be established before their use in clinical research. Four kinds of amphiphilic polymeric (PEG-PG-PCL, PEEP-PCL, PEG-PCL and PEG-DSPE) micelles with similar hydrophilic or hydrophobic structure were prepared and their in vitro and in vivo safety were evaluated and compared. In vitro nanotoxicity evaluations included assessments of cell morphology, cell volume, inflammatory effects, cytotoxicity, apoptosis and membrane fluidity. An umbilical vein cell line (Eahy.926) and a kind of macrophages (J774.A1) were used as cell models considering that intravenous route is dominant for micelle delivery systems. In vivo analyses included complete blood count, lymphocyte subset analysis, detection of plasma inflammatory factors and histological observations of major organs after intravenous administration to KM mice. All the micelles enhanced inflammatory molecules in J774.A1 cells, likely resulting from the increased ROS levels. PEG-PG-PCL and PEEP-PCL micelles were found to increase the J774.A1 cell volume. This likely correlated with the size of PEG-PG-PCL micelles and the polyphosphoester structure in PEEP-PCL. PEG-DSPE micelles inhibited the growth of Eahy.926 cells via inducing apoptosis. This might relate to the structure of DSPE, which is a type of phospholipid and has good affinity with cell membrane. No evidence was found for cell membrane changes after treatment with these micelles for 24 h. In the in vivo study, during 8 days of 4 time injection, each of the four nanocarriers altered the hematic phase differently without changes in inflammatory factors or pathological changes in target organs. These results demonstrate that the micelles investigated exhibit diverse nanotoxicity correlated with their structures, their biosafety is different in different cell model, and there is no in vitro and in vivo correlation found. We believe that this study will certainly provide more

  19. Novel amphiphiles with preorganized functionalities-formation of Langmuir-films and efficiency in mineral flotation.

    Science.gov (United States)

    Müller, P U; Akpo, C C; Stöckelhuber, K W; Weber, E

    2005-06-30

    Based on the principle of supramolecular preorganization, three different types of new oligofunctional surfactants have been designed and prepared differing in both the degree of conformational flexibility and the hydrophilic-lipophilic balance of their structures due to the chosen building blocks including rather rigid and shape-persistent backbones or a dendritic subunit. Surface-active properties of the oligofunctional surfactants involving critical micellization concentration, surface tension at cmc, effectiveness of surface tension reduction, and the efficiency of adsorption were determined by use of the surface tension isotherms, respectively. In particular the amino-acid-based amphiphiles show remarkable surface-active properties with the adsorption at the air/water interface and also the aggregation to micelles starting at very low concentration. By analysis of the surface pressure-surface area isotherms interesting information on the packing behavior and orientation of the amphiphilic molecules in relation to the molecular structure could be obtained. Moreover, limiting area and collapse pressure of the Langmuir-films were determined. Morphological observation of the dynamic process of monolayer compression at the air/water interface was carried out by Brewster angle microscopy illustrating several phase states visualized as snap shots. Furthermore, the effectiveness of the new surfactants acting as collecting agents in the process of flotation using the model mineral fluorite was studied. A surprisingly high recovery of the mineral was obtained for the surfactants with constricted flexibility. The flotation plots clearly manifest that bundling of surfactant subunits by tethering to an aromatic core or by dendritic branching is profitable, indicating that effects of preorganization of the oligofunctional surfactant molecules are important.

  20. Recognition of GPCRs by peptide ligands and membrane compartments theory: structural studies of endogenous peptide hormones in membrane environment.

    Science.gov (United States)

    Sankararamakrishnan, Ramasubbu

    2006-04-01

    One of the largest family of cell surface proteins, G-protein coupled receptors (GPCRs) regulate virtually all known physiological processes in mammals. With seven transmembrane segments, they respond to diverse range of extracellular stimuli and represent a major class of drug targets. Peptidergic GPCRs use endogenous peptides as ligands. To understand the mechanism of GPCR activation and rational drug design, knowledge of three-dimensional structure of receptor-ligand complex is important. The endogenous peptide hormones are often short, flexible and completely disordered in aqueous solution. According to "Membrane Compartments Theory", the flexible peptide binds to the membrane in the first step before it recognizes its receptor and the membrane-induced conformation is postulated to bind to the receptor in the second step. Structures of several peptide hormones have been determined in membrane-mimetic medium. In these studies, micelles, reverse micelles and bicelles have been used to mimic the cell membrane environment. Recently, conformations of two peptide hormones have also been studied in receptor-bound form. Membrane environment induces stable secondary structures in flexible peptide ligands and membrane-induced peptide structures have been correlated with their bioactivity. Results of site-directed mutagenesis, spectroscopy and other experimental studies along with the conformations determined in membrane medium have been used to interpret the role of individual residues in the peptide ligand. Structural differences of membrane-bound peptides that belong to the same family but differ in selectivity are likely to explain the mechanism of receptor selectivity and specificity of the ligands. Knowledge of peptide 3D structures in membrane environment has potential applications in rational drug design.

  1. Therapeutic HIV Peptide Vaccine

    DEFF Research Database (Denmark)

    Fomsgaard, Anders

    2015-01-01

    Therapeutic vaccines aim to control chronic HIV infection and eliminate the need for lifelong antiretroviral therapy (ART). Therapeutic HIV vaccine is being pursued as part of a functional cure for HIV/AIDS. We have outlined a basic protocol for inducing new T cell immunity during chronic HIV-1...... infection directed to subdominant conserved HIV-1 epitopes restricted to frequent HLA supertypes. The rationale for selecting HIV peptides and adjuvants are provided. Peptide subunit vaccines are regarded as safe due to the simplicity, quality, purity, and low toxicity. The caveat is reduced immunogenicity...

  2. Peptide Vaccine Against Paracoccidioidomycosis.

    Science.gov (United States)

    Taborda, Carlos P; Travassos, Luiz R

    2017-01-01

    The chapter reviews methods utilized for the isolation and characterization of a promising immunogen candidate, aiming at a human vaccine against paracoccidioidomycosis. Peptide P10 carries a T-CD4+ epitope and was identified as an internal sequence of the major diagnostic antigen known as gp43 glycoprotein. It successfully treated massive intratracheal infections by virulent Paracoccidioides brasiliensis in combination with chemotherapy.An introduction about the systemic mycosis was found essential to understand the various options that were considered to design prophylactic and therapeutic vaccine protocols using peptide P10.

  3. High-throughput development of amphiphile self-assembly materials: fast-tracking synthesis, characterization, formulation, application, and understanding.

    Science.gov (United States)

    Mulet, Xavier; Conn, Charlotte E; Fong, Celesta; Kennedy, Danielle F; Moghaddam, Minoo J; Drummond, Calum J

    2013-07-16

    Amphiphile self-assembly materials, which contain both a hydrophilic and a hydrophobic domain, have great potential in high-throughput and combinatorial approaches to discovery and development. However, the materials chemistry community has not embraced these ideas to anywhere near the extent that the medicinal chemistry community has. While this situation is beginning to change, extracting the full potential of high-throughput approaches in the development of self-assembling materials will require further development in the synthesis, characterization, formulation, and application domains. One of the key factors that make small molecule amphiphiles prospective building blocks for next generation multifunctional materials is their ability to self-assemble into complex nanostructures through low-energy transformations. Scientists can potentially tune, control, and functionalize these structures, but only after establishing their inherent properties. Because both robotic materials handling and customized rapid characterization equipment are increasingly available, high-throughput solutions are now attainable. These address traditional development bottlenecks associated with self-assembling amphiphile materials, such as their structural characterization and the assessment of end-use functional performance. A high-throughput methodology can help streamline materials development workflows, in accord with existing high-throughput discovery pipelines such as those used by the pharmaceutical industry in drug discovery. Chemists have identified several areas that are amenable to a high-throughput approach for amphiphile self-assembly materials development. These allow an exploration of not only a large potential chemical, compositional, and structural space, but also material properties, formulation, and application variables. These areas of development include materials synthesis and preparation, formulation, characterization, and screening performance for the desired end

  4. Simulation of Peptide Binding to Silica and Silica Mineralization

    Science.gov (United States)

    Emami, F. S.; Heinz, H.; Berry, R. J.; Varshney, V.; Farmer, B. L.; Naik, R. R.; Patwardhan, S. V.; Perry, C. C.

    2009-03-01

    The purpose of this study is to identify the nature of the interaction of peptides with silica surfaces and their effect on mineralization. Classical force fields (CVFF, PCFF) have been extended for silica aiming at the computation of surface properties in quantitative agreement with experiment, taking explicitly into account water molecules, pH, and surface coverage with peptides. We focus on the interaction of five short peptides (pep1, pep4, 82-4, H4, R5) identified by biopanning with regular and amorphous silica surfaces (Q3 and Q2) to understand the relation between peptide sequence and affinity to the surface. Results of the atomistic molecular dynamics simulation indicate adsorption energies, binding constants and conformational changes upon adsorption. The comparison of NMR chemical shifts in solution and on the surface in computation and experiment further aids in understanding the mechanism of binding.

  5. Critical Assessment of Current Force Fields. Short Peptide Test Case

    Czech Academy of Sciences Publication Activity Database

    Vymětal, Jiří; Vondrášek, Jiří

    2013-01-01

    Roč. 9, č. 1 (2013), s. 441-451 ISSN 1549-9618 R&D Projects: GA MŠk(CZ) LH11020 Grant - others:GA MŠk(CZ) LM2010005 Institutional support: RVO:61388963 Keywords : Helix-coil transition * protein-folding simulations * amino-acids * side-chain * alanine dipeptide Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 5.310, year: 2013

  6. Aggregation properties of a short peptide that mediates amyloid fibril ...

    Indian Academy of Sciences (India)

    Mandelkow E 2005 Tau aggregation is driven by a transition from random coil to beta sheet structure. Biochim. Biophys. Acta 1739 158–166 von Bergen M, Barghorn S, Li L, Marx A, Biernat J, Mandelkow. EM and Mandelkow E 2001 Mutations of tau protein in frontotemporal dementia promote aggregation of paired helical.

  7. A short history of neuroendocrine tumours and their peptide hormones

    DEFF Research Database (Denmark)

    de Herder, Wouter W; Rehfeld, Jens F; Kidd, Mark

    2016-01-01

    The discovery of neuroendocrine tumours of the gastrointestinal tract and pancreas started in 1870, when Rudolf Heidenhain discovered the neuroendocrine cells, which can lead to the development of these tumours. Siegfried Oberndorfer was the first to introduce the term carcinoid in 1907. The panc...

  8. Short monolithic columns for purification and fractionation of peptide samples

    Czech Academy of Sciences Publication Activity Database

    Moravcová, Dana; Kahle, Vladislav; Řehulková, Helena; Chmelík, Jan; Řehulka, Pavel

    2009-01-01

    Roč. 1216, č. 17 (2009), s. 3629-3636 ISSN 0021-9673 R&D Projects: GA MŠk LC06023; GA MŠk 1M06030; GA ČR GA203/06/1179; GA AV ČR IAAX00310701 Institutional research plan: CEZ:AV0Z40310501 Keywords : proteomics * monolithic capillary columns * sample pre-treatment Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 4.101, year: 2009

  9. Co-assembly, spatiotemporal control and morphogenesis of a hybrid protein-peptide system

    Science.gov (United States)

    Inostroza-Brito, Karla E.; Collin, Estelle; Siton-Mendelson, Orit; Smith, Katherine H.; Monge-Marcet, Amàlia; Ferreira, Daniela S.; Rodríguez, Raúl Pérez; Alonso, Matilde; Rodríguez-Cabello, José Carlos; Reis, Rui L.; Sagués, Francesc; Botto, Lorenzo; Bitton, Ronit; Azevedo, Helena S.; Mata, Alvaro

    2015-11-01

    Controlling molecular interactions between bioinspired molecules can enable the development of new materials with higher complexity and innovative properties. Here we report on a dynamic system that emerges from the conformational modification of an elastin-like protein by peptide amphiphiles and with the capacity to access, and be maintained in, non-equilibrium for substantial periods of time. The system enables the formation of a robust membrane that displays controlled assembly and disassembly capabilities, adhesion and sealing to surfaces, self-healing and the capability to undergo morphogenesis into tubular structures with high spatiotemporal control. We use advanced microscopy along with turbidity and spectroscopic measurements to investigate the mechanism of assembly and its relation to the distinctive membrane architecture and the resulting dynamic properties. Using cell-culture experiments with endothelial and adipose-derived stem cells, we demonstrate the potential of this system to generate complex bioactive scaffolds for applications such as tissue engineering.

  10. NCAM Mimetic Peptides: An Update

    DEFF Research Database (Denmark)

    Berezin, Vladimir; Bock, Elisabeth

    2008-01-01

    of combinatorial peptide libraries. The C3 and NBP10 peptides target the first Ig module whereas the ENFIN2 and ENFIN11 peptides target fibronectin type III (FN3) modules of NCAM. A number of NCAM mimetics can induce neurite outgrowth and exhibit neuroprotective and synaptic plasticity modulating properties...

  11. brain natriuretic peptide

    African Journals Online (AJOL)

    Background: Recently brain natriuretic peptide (BNP) level has been introduced as a screening test for congestive heart failure (CHF) in children. The current CHF assessment scores are not satisfactory as they use a large number of variables. Objective: To evaluate two CHF scores: a modified clinical score and an echo-.

  12. Brain Peptides and Psychopharmacology

    Science.gov (United States)

    Arehart-Treichel, Joan

    1976-01-01

    Proteins isolated from the brain and used as drugs can improve and apparently even transfer mental states and behavior. Much of the pioneering work and recent research with humans and animals is reviewed and crucial questions that are being posed about the psychologically active peptides are related. (BT)

  13. ARA-PEPs: a repository of putative sORF-encoded peptides in Arabidopsis thaliana.

    Science.gov (United States)

    Hazarika, Rashmi R; De Coninck, Barbara; Yamamoto, Lidia R; Martin, Laura R; Cammue, Bruno P A; van Noort, Vera

    2017-01-17

    Many eukaryotic RNAs have been considered non-coding as they only contain short open reading frames (sORFs). However, there is increasing evidence for the translation of these sORFs into bioactive peptides with potent signaling, antimicrobial, developmental, antioxidant roles etc. Yet only a few peptides encoded by sORFs are annotated in the model organism Arabidopsis thaliana. To aid the functional annotation of these peptides, we have developed ARA-PEPs (available at http://www.biw.kuleuven.be/CSB/ARA-PEPs ), a repository of putative peptides encoded by sORFs in the A. thaliana genome starting from in-house Tiling arrays, RNA-seq data and other publicly available datasets. ARA-PEPs currently lists 13,748 sORF-encoded peptides with transcriptional evidence. In addition to existing data, we have identified 100 novel transcriptionally active regions (TARs) that might encode 341 novel stress-induced peptides (SIPs). To aid in identification of bioactivity, we add functional annotation and sequence conservation to predicted peptides. To our knowledge, this is the largest repository of plant peptides encoded by sORFs with transcript evidence, publicly available and this resource will help scientists to effortlessly navigate the list of experimentally studied peptides, the experimental and computational evidence supporting the activity of these peptides and gain new perspectives for peptide discovery.

  14. Glucagon-like peptide 1 receptor agonist (GLP-1 RA)

    DEFF Research Database (Denmark)

    von Scholten, Bernt Johan; Hansen, Tine Willum; Goetze, Jens Peter

    2015-01-01

    AIMS: In a short-term study including 31 patients with type 2 diabetes, glucagon-like peptide 1 receptor agonist (GLP-1 RA) treatment was associated with a significant reversible decline in GFR. Twenty-three patients re-initiated GLP-1 RA treatment after the primary study, and the aim...

  15. Optimization of antibacterial peptides by genetic algorithms and cheminformatics

    DEFF Research Database (Denmark)

    Fjell, Christopher D.; Jenssen, Håvard; Cheung, Warren A.

    2011-01-01

    Pathogens resistant to available drug therapies are a pressing global health problem. Short, cationic peptides represent a novel class of agents that have lower rates of drug resistance than derivatives of current antibiotics. Previously, we created a software system utilizing artificial neural...

  16. Photoperiod Regulates vgf-Derived Peptide Processing in Siberian Hamsters.

    Directory of Open Access Journals (Sweden)

    Barbara Noli

    Full Text Available VGF mRNA is induced in specific hypothalamic areas of the Siberian hamster upon exposure to short photoperiods, which is associated with a seasonal decrease in appetite and weight loss. Processing of VGF generates multiple bioactive peptides, so the objective of this study was to determine the profile of the VGF-derived peptides in the brain, pituitary and plasma from Siberian hamsters, and to establish whether differential processing might occur in the short day lean state versus long day fat. Antisera against short sequences at the C- or N- termini of proVGF, as well as against NERP-1, TPGH and TLQP peptides, were used for analyses of tissues, and both immunohistochemistry and enzyme linked immunosorbent assay (ELISA coupled with high-performance liquid (HPLC or gel chromatography were carried out. VGF peptide immunoreactivity was found within cortex cholinergic perikarya, in multiple hypothalamic nuclei, including those containing vasopressin, and in pituitary gonadotrophs. ELISA revealed that exposure to short day photoperiod led to a down-regulation of VGF immunoreactivity in the cortex, and a less pronounced decrease in the hypothalamus and pituitary, while the plasma VGF levels were not affected by the photoperiod. HPLC and gel chromatography both confirmed the presence of multiple VGF-derived peptides in these tissues, while gel chromatography showed the presence of the VGF precursor in all tissues tested except for the cortex. These observations are consistent with the view that VGF-derived peptides have pleiotropic actions related to changing photoperiod, possibly by regulating cholinergic systems in the cortex, vasopressin hypothalamic pathways, and the reproductive axis.

  17. [Biosynthesis of opioid peptides].

    Science.gov (United States)

    Rossier, J

    1988-01-01

    The endogenous opioid peptides all contain the enkephalin sequence Tyr-Gly-Gly-Phe-Met and Tyr-Gly-Gly-Phe-Leu at their aminoterminus. Three distinct families of these peptides (endorphins, enkephalins and dynorphins) are present in different neuronal pathways within the central nervous system. Molecular genetics have shown that these three families of opioid peptides are derived from three distinct precursors. Pro-opiomelanocortin gives rise to the endorphins, as well as adrenocorticotropic hormone (ACTH) and the melanotropic hormones (MSH's). [Met] enkephalin, [Leu] enkephalin and the related heptapeptide [Met] enkephalin-Arg6-Phe7 and octapeptide [Met] enkephalin-Arg6-Gly7-Leu8 are derived from proenkephalin. The third family is derived from prodynorphin and includes dynorphin A, dynorphin B (also known as rimorphin) and alpha- and beta-neo-endorphin. The structure of the genes coding for these precursors are similar, suggesting the possibility of one common ancestral gene. The most common scheme for enzymatic maturation of precursors proposes the action of a trypsin-like endopeptidase followed by a carboxypeptidase B-like exopeptidase. However, we have provided evidence that this combination of trypsin-like and carboxypeptidase B-like enzymes may not be the only mechanism for liberating enkephalin from low molecular weight enkephalin-containing peptides. Indeed, endo-oligopeptidase A, an enzyme, known to hydrolyze the Phe5-Ser6 bond of bradykinin and the Arg8-Arg9 bond of neurotensin, has been shown to produce, by a single cleavage, [Leu] enkephalin or [Met] enkephalin from small enkephalin-containing peptides, (Camargo et al., 1987, J. Neurochem. 48, 1258-1263).(ABSTRACT TRUNCATED AT 250 WORDS)

  18. Biochemical functionalization of peptide nanotubes with phage displayed peptides

    Science.gov (United States)

    Swaminathan, Swathi; Cui, Yue

    2016-09-01

    The development of a general approach for the biochemical functionalization of peptide nanotubes (PNTs) could open up existing opportunities in both fundamental studies as well as a variety of applications. PNTs are spontaneously assembled organic nanostructures made from peptides. Phage display has emerged as a powerful approach for identifying selective peptide binding motifs. Here, we demonstrate for the first time the biochemical functionalization of PNTs via peptides identified from a phage display peptide library. The phage-displayed peptides are shown to recognize PNTs. These advances further allow for the development of bifunctional peptides for the capture of bacteria and the self-assembly of silver particles onto PNTs. We anticipate that these results could provide significant opportunities for using PNTs in both fundamental studies and practical applications, including sensors and biosensors nanoelectronics, energy storage devices, drug delivery, and tissue engineering.

  19. Molecular mechanism of synergy between the antimicrobial peptides PGLa and magainin 2.

    Science.gov (United States)

    Zerweck, Jonathan; Strandberg, Erik; Kukharenko, Olga; Reichert, Johannes; Bürck, Jochen; Wadhwani, Parvesh; Ulrich, Anne S

    2017-10-13

    PGLa and magainin 2 (MAG2) are amphiphilic α-helical membranolytic peptides from frog skin with known synergistic antimicrobial activity. By systematically mutating residues in the two peptides it was possible to identify the ones crucial for the synergy, as monitored by biological assays, fluorescence vesicle leakage, and solid-state 15 N-NMR. Electrostatic interactions between anionic groups in MAG2 and cationic residues in PGLa enhance synergy but are not necessary for the synergistic effect. Instead, two Gly residues (7 and 11) in a so-called GxxxG motif in PGLa are necessary for synergy. Replacing either of them with Ala or another hydrophobic residue completely abolishes synergy according to all three methods used. The designer-made peptide MSI-103, which has a similar sequence as PGLa, shows no synergy with MAG2, but by introducing two Gly mutations it was possible to make it synergistic. A molecular model is proposed for the functionally active PGLa-MAG2 complex, consisting of a membrane-spanning antiparallel PGLa dimer that is stabilized by intimate Gly-Gly contacts, and where each PGLa monomer is in contact with one MAG2 molecule at its C-terminus.

  20. Towards the Development of Synthetic Antibiotics: Designs Inspired by Natural Antimicrobial Peptides.

    Science.gov (United States)

    Azmi, Fazren; Skwarczynski, Mariusz; Toth, Istvan

    2016-01-01

    Virtually every living organism produces gene-encoded antimicrobial peptides (AMPs) that provide an immediate defence against pathogen invasion. Many AMPs have been isolated and used as antibiotics that are effective against multidrug-resistant bacteria. Although encouraging, AMPs have such poor drug-like properties that their application for clinical use is restricted. In turn, this has diverted research to the development of synthetic molecules that retain the therapeutic efficacy of AMPs but are endowed with greater biological stability and safety profiles. Most of the synthetic molecules, either based on a peptidic or non-peptidic scaffold, have been designed to mimic the amphiphilic properties of native AMPs, which are widely believed to be the key determinant of their antibacterial activity. In this review, the structural, chemical and biophysical features that govern the biological activities of various synthetic designs are discussed extensively. Recent innovative approaches from the literature that exhibit novel concepts towards the development of new synthetic antibacterial agents, including the engineered delivery platform incorporated with AMP mimetics, are also emphasised.

  1. Mechanism of bacterial membrane poration by Antimicrobial Peptides

    Science.gov (United States)

    Arora, Ankita; Mishra, Abhijit

    2015-03-01

    Bacterial resistance to conventional antibiotics is a major health concern. Antimicrobial peptides (AMPs), an important component of mammalian immune system, are thought to utilize non-specific interactions to target common features on the outer membranes of pathogens; hence development of resistance to such AMPs may be less pronounced. Most AMPs are amphiphilic and cationic in nature. Most AMPs form pores in the bacterial membranes causing them to lyse, however, the exact mechanism is unknown. Here, we study the AMP CHRG01 (KSSTRGRKSSRRKK), derived from human β defensin 3 (hBD3) with all Cysteine residues substituted with Serine. Circular Dichorism studies indicate that CHRG01 shows helicity and there is change in helicity as it interacts with the lipid membrane. The AMP was effective against different species of bacteria. Leakage of cellular components from bacterial cells observed by SEM and AFM indicates AMP action by pore formation. Confocal microscopy studies on giant vesicles incubated with AMP confirm poration. The effect of this AMP on model bacterial membranes is characterized using Small Angle X-ray scattering and Fluorescence spectroscopy to elucidate the mechanism behind antimicrobial activity.

  2. The dynamic self-assembly of peptides into nanostructures

    Science.gov (United States)

    Perumal, Shiamalee

    Progress in the new and interdisciplinary field of biophysics holds great promise for new understandings and practical applications. Applying the methods of physics and chemistry to biological systems provides us with a valuable insight into the fundamental processes of life. In this study, the advanced physical techniques of neutron reflection and small-angle neutron scattering are applied to investigate the dynamic self-assembly of peptide systems at the solid-liquid and air-liquid interface, and in bulk solution. The characterisation of various peptides and an in-depth evaluation of their interfacial structural conformations and their outstanding ability to form well-defined nanostructures in aqueous solution will be presented in this thesis. The key adsorption factors of peptide concentration, solution pH, temperature, salt addition, and time were found to have imperative and varying effects on these self-assembled peptide structures. The hydrophobic nature of certain ?-sheet forming peptides resulted in an adsorption where the peptides were predominantly afloat on the surface of water. Point mutations of four other analogously designed peptides were reported to self-assemble into either ?-helix or ?-sheet secondary structures in order of increasing hydrophobicity. Short ionic peptides that had the potential to solubilise and stabilise membrane proteins were also discovered to self-assemble into aqueous solution to form a co-existing mixture of nanotube and nanovesicle structures of varying diversity with an unwavering bilayer wall thickness also consistent with interfacial structural parameters. These self-assembled peptide conformations were of course highly dependent on solution conditions and on the physical properties of the interface.

  3. Stepwise-activable multifunctional peptide-guided prodrug micelles for cancerous cells intracellular drug release

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Jing, E-mail: zhangjing@zjut.edu.cn; Li, Mengfei [Zhejiang University of Technology, College of Materials Science and Engineering (China); Yuan, Zhefan [Zhejiang University, Key Laboratory of Biomass Chemical Engineering of Ministry of Education, Department of Chemical and Biological Engineering (China); Wu, Dan; Chen, Jia-da; Feng, Jie, E-mail: fengjie@zjut.edu.cn [Zhejiang University of Technology, College of Materials Science and Engineering (China)

    2016-10-15

    A novel type of stepwise-activable multifunctional peptide-guided prodrug micelles (MPPM) was fabricated for cancerous cells intracellular drug release. Deca-lysine sequence (K{sub 10}), a type of cell-penetrating peptide, was synthesized and terminated with azido-glycine. Then a new kind of molecule, alkyne modified doxorubicin (DOX) connecting through disulfide bond (DOX-SS-alkyne), was synthesized. After coupling via Cu-catalyzed azide–alkyne cycloaddition (CuAAC) click chemistry reaction, reduction-sensitive peptide-guided prodrug was obtained. Due to the amphiphilic property of the prodrug, it can assemble to form micelles. To prevent the nanocarriers from unspecific cellular uptake, the prodrug micelles were subsequently modified with 2,3-dimethyl maleic anhydride to obtain MPPM with a negatively charged outer shell. In vitro studies showed that MPPM could be shielded from cells under psychological environment. However, when arriving at mild acidic tumor site, the cell-penetrating capacity of MPPM would be activated by charge reversal of the micelles via hydrolysis of acid-labile β-carboxylic amides and regeneration of K{sub 10}, which enabled efficient internalization of MPPM by tumor cells as well as following glutathione- and protease-induced drug release inside the cancerous cells. Furthermore, since the guide peptide sequences can be accurately designed and synthesized, it can be easily changed for various functions, such as targeting peptide, apoptotic peptide, even aptamers, only need to be terminated with azido-glycine. This method can be used as a template for reduction-sensitive peptide-guided prodrug for cancer therapy.Graphical abstractA novel type of stepwise-activable multifunctional peptide-guided prodrug micelles (MPPM) was fabricated for selective drug delivery in cancerous cells. MPPM could be shielded from cells under psychological environment. However, when arriving at mild acidic tumor site, the cell-penetrating capacity of MPPM would

  4. Ga(III) chelates of amphiphilic DOTA-based ligands: synthetic route and in vitro and in vivo studies

    Energy Technology Data Exchange (ETDEWEB)

    Fontes, Andre [Centro de Quimica, Campus de Gualtar, Universidade do Minho, 4710-057, Braga (Portugal); Prata, M. Isabel M. [IBILI, Faculdade de Medicina, Universidade de Coimbra, 3548, Coimbra (Portugal); Geraldes, Carlos F.G.C. [Departamento de Ciencias da Vida, Faculdade de Ciencias e Tecnologia, Universidade de Coimbra, 3001-401, Coimbra (Portugal); Centro de Neurociencias e Biologia Celular, Universidade de Coimbra, 3001-401, Coimbra (Portugal); Andre, Joao P., E-mail: jandre@quimica.uminho.p [Centro de Quimica, Campus de Gualtar, Universidade do Minho, 4710-057, Braga (Portugal)

    2011-04-15

    In this work, we report on a synthetic strategy using amphiphilic DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid)-based chelators bearing a variable-sized {alpha}-alkyl chain at one of the pendant acetate arms (from 6 to 14 carbon atoms), compatible with their covalent coupling to amine-bearing biomolecules. The amphiphilic behavior of the micelles-forming Ga(III) chelates (critical micellar concentration), their stability in blood serum and their lipophilicity (logP) were investigated. Biodistribution studies with the {sup 67}Ga-labeled chelates were performed in Wistar rats, which showed a predominant liver uptake with almost no traces of the radiochelates in the body after 24 h.

  5. Graphene oxide-enhanced sol-gel transition sensitivity and drug release performance of an amphiphilic copolymer-based nanocomposite

    Science.gov (United States)

    Hu, Huawen; Wang, Xiaowen; Lee, Ka I; Ma, Kaikai; Hu, Hong; Xin, John H.

    2016-01-01

    We report the fabrication of a highly sensitive amphiphilic copolymer-based nanocomposite incorporating with graphene oxide (GO), which exhibited a low-intensity UV light-triggered sol-gel transition. Non-cytotoxicity was observed for the composite gels after the GO incorporation. Of particular interest were the microchannels that were formed spontaneously within the GO-incorporated UV-gel, which expedited sustained drug release. Therefore, the present highly UV-sensitive, non-cytotoxic amphiphilic copolymer-based composites is expected to provide enhanced photothermal therapy and chemotherapy by means of GO’s unique photothermal properties, as well as through efficient passive targeting resulting from the sol-gel transition characteristic of the copolymer-based system with improved sensitivity, which thus promises the enhanced treatment of patients with cancer and other diseases. PMID:27539298

  6. One-Pot Synthesis of (+-Nootkatone via Dark Singlet Oxygenation of Valencene: The Triple Role of the Amphiphilic Molybdate Catalyst

    Directory of Open Access Journals (Sweden)

    Bing Hong

    2016-11-01

    Full Text Available Efficient one-pot catalytic synthesis of (+-nootkatone was performed from (+-valencene using only hydrogen peroxide and amphiphilic molybdate ions. The process required no solvent and proceeded in three cascade reactions: (i singlet oxygenation of valencene according to the ene reaction; (ii Schenck rearrangement of one hydroperoxide into the secondary β-hydroperoxide; and (iii dehydration of the hydroperoxide into the desired (+-nootkatone. The solvent effect on the hydroperoxide rearrangement is herein discussed. The amphiphilic dimethyldioctyl ammonium molybdate, which is also a balanced surfactant, played a triple role in this process, as molybdate ions catalyzed at both Step 1 and Step 3 and it allowed the rapid formation of a three-phase microemulsion system that highly facilitates product recovery. Preparative synthesis of the high added value (+-nootkatone was thus performed at room temperature with an isolated yield of 46.5%. This is also the first example of a conversion of allylic hydroperoxides into ketones catalyzed by molybdate ions.

  7. Coulomb repulsion in short polypeptides.

    Science.gov (United States)

    Norouzy, Amir; Assaf, Khaleel I; Zhang, Shuai; Jacob, Maik H; Nau, Werner M

    2015-01-08

    Coulomb repulsion between like-charged side chains is presently viewed as a major force that impacts the biological activity of intrinsically disordered polypeptides (IDPs) by determining their spatial dimensions. We investigated short synthetic models of IDPs, purely composed of ionizable amino acid residues and therefore expected to display an extreme structural and dynamic response to pH variation. Two synergistic, custom-made, time-resolved fluorescence methods were applied in tandem to study the structure and dynamics of the acidic and basic hexapeptides Asp6, Glu6, Arg6, Lys6, and His6 between pH 1 and 12. (i) End-to-end distances were obtained from the short-distance Förster resonance energy transfer (sdFRET) from N-terminal 5-fluoro-l-tryptophan (FTrp) to C-terminal Dbo. (ii) End-to-end collision rates were obtained for the same peptides from the collision-induced fluorescence quenching (CIFQ) of Dbo by FTrp. Unexpectedly, the very high increase of charge density at elevated pH had no dynamical or conformational consequence in the anionic chains, neither in the absence nor in the presence of salt, in conflict with the common view and in partial conflict with accompanying molecular dynamics simulations. In contrast, the cationic peptides responded to ionization but with surprising patterns that mirrored the rich individual characteristics of each side chain type. The contrasting results had to be interpreted, by considering salt screening experiments, N-terminal acetylation, and simulations, in terms of an interplay of local dielectric constant and peptide-length dependent side chain charge-charge repulsion, side chain functional group solvation, N-terminal and side chain charge-charge repulsion, and side chain-side chain as well as side chain-backbone interactions. The common picture that emerged is that Coulomb repulsion between water-solvated side chains is efficiently quenched in short peptides as long as side chains are not in direct contact with each

  8. Highly ordered self-assembly of one-dimensional nanoparticles in amphiphilic molecular systems

    International Nuclear Information System (INIS)

    Kim, Tae Hwan

    2009-02-01

    Two kinds of one-dimensional (1D) nanoparticles, stable rod-like nanoparticles with highly controlled surface charge density (cROD) and non-covalently functionalized isolated single wall carbon nanotubes (p-SWNT) that were readily redispersible in water, have been developed. Using these 1D nanoparticles, various highly ordered superstructures of 1D nanoparticles by molecular self-assembling based on electrostatic interaction in amphiphilic molecular systems (two different cationic liposome systems) have been investigated. To our knowledge, this is the first demonstration of highly ordered self-assembly of 1D nanoparticles based on electrostatic interaction between 1D nanoparticles and amphiphilic molecules. The cRODs have been developed by free radical polymerization of a mixture of polymerizable cationic surfactant, cetyltrimethylammonium 4-vinylbenzoate (CTVB), and hydrotropic salt sodium 4-styrenesulfonate (NaSS) in aqueous solution. The surface charge of the cROD was controlled by varying the NaSS concentration during the polymerization process and the charge variation was interpreted in terms of the overcharging effect in colloidal systems. The small angle neutron scattering (SANS) measurements showed that the diameter of cROD is constant at 4 nm and the particle length ranges from 20 nm to 85 nm, depending on the NaSS concentration. The cRODs are longest when the NaSS concentration is 5 mol % which corresponds to the charge inversion or neutral point. The SANS and zeta potential measurements showed that the Coulomb interactions between the particles are strongly dependent on the NaSS concentration and the zeta potential of the cRODs changes from positive to negative (+ 12.8 mV ∼ - 44.2 mV) as the concentration of NaSS increases from 0 mol % to 40 mol %. As the NaSS concentration is further increased, the zeta potential is saturated at approximately - 50 mV. The p-SWNTs have been developed by 1) dispersing single wall carbon nanotubes (SWNTs) in water using

  9. Oligonucleotides conjugated to short lysine chains.

    Science.gov (United States)

    Winkler, Johannes; Urban, Ernst; Noe, Christian R

    2005-01-01

    A new method for synthesizing oligonucleotide peptide conjugates by an in-line approach is presented. A phosphorothioate oligonucleotide with the sequence of bcl-2 targeted Oblimersen by employing a modified 2'-amino-2'-desoxy-uridine nucleotide bearing a succinyl linker at the 2' position was prepared. The carboxyl group was protected for solid-phase synthesis as the benzyl ester. Ester cleavage was afforded by a phase transfer reaction using palladium nanoparticles as catalyst and cyclohexadiene as hydrogen donor. Short tails of up to three lysyl residues were conjugated to the oligonucleotide by an inverse stepwise peptide synthesis. The conjugates were characterized by HPLC, mass spectrometry, and circular dichroism. Influence of lysyl tails on CD spectra were minimal. Melting profiles revealed only minimal destabilizing effects on duplexes by conjugation of peptides.

  10. Antibody Production with Synthetic Peptides.

    Science.gov (United States)

    Lee, Bao-Shiang; Huang, Jin-Sheng; Jayathilaka, Lasanthi P; Lee, Jenny; Gupta, Shalini

    2016-01-01

    Peptides (usually 10-20 amino acid residues in length) can be used as effectively as proteins in raising antibodies producing both polyclonal and monoclonal antibodies routinely with titers higher than 20,000. Peptide antigens do not function as immunogens unless they are conjugated to proteins. Production of high quality antipeptide antibodies is dependent upon peptide sequence selection, the success of peptide synthesis, peptide-carrier protein conjugation, the humoral immune response in the host animal, the adjuvant used, the peptide dose administered, the injection method, and the purification of the antibody. Peptide sequence selection is probably the most critical step in the production of antipeptide antibodies. Although the process for designing peptide antigens is not exact, several guidelines and computational B-cell epitope prediction methods can help maximize the likelihood of producing antipeptide antibodies that recognize the protein. Antibodies raised by peptides have become essential tools in life science research. Virtually all phospho-specific antibodies are now produced using phosphopeptides as antigens. Typically, 5-20 mg of peptide is enough for antipeptide antibody production. It takes 3 months to produce a polyclonal antipeptide antibody in rabbits that yields ~100 mL of serum which corresponds to ~8-10 mg of the specific antibody after affinity purification using a peptide column.

  11. Bombesin peptide antagonist for target-selective delivery of liposomal doxorubicin on cancer cells.

    Science.gov (United States)

    Accardo, Antonella; Mansi, Rosalba; Salzano, Giuseppina; Morisco, Anna; Aurilio, Michela; Parisi, Antonio; Maione, Francesco; Cicala, Carla; Ziaco, Barbara; Tesauro, Diego; Aloj, Luigi; De Rosa, Giuseppe; Morelli, Giancarlo

    2012-11-21

    Purpose: This study addresses novel peptide modified liposomal doxorubicin to specifically target tissues overexpressing bombesin (BN) receptors. Methods: DOTA-(AEEA)(2)-peptides containing the [7-14]bombesin and the new BN-AA1 sequence have been synthesized to compare their binding properties and in serum stabilities. The amphiphilic peptide derivative (MonY-BN-AA1) containing BN-AA1, a hydrophobic moiety, polyethylenglycole (PEG), and diethylenetriaminepentaacetate (DTPA), has been synthesized. Liposomes have been obtained by mixing of MonY-BN-AA1 with 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC). Results: Both (111)In labeled peptide derivatives present nanomolar Kd to PC-3 cells. (177)Lu labeled peptide DOTA-(AEEA)(2)-BN-AA1 is very stable (half-life 414.1 h), while DOTA-(AEEA)(2)-BN, shows a half-life of 15.5 h. In vivo studies on the therapeutic efficacy of DSPC/MonY-BN-AA1/Dox in comparison to DSPC/MonY-BN/Dox, were performed in PC-3 xenograft bearing mice. Both formulations showed similar tumor growth inhibition (TGI) compared to control animals treated with non-targeted DSPC/Dox liposomes or saline solution. For DSPC/MonY-BN-AA1/Dox the maximum effect was observed 19 days after treatment. Conclusions: DSPC/MonY-BN-AA1/Dox nanovectors confirm the ability to selectively target and provide therapeutic efficacy in mice. The lack of receptor activation and possible acute biological side effects provided by using the AA1 antagonist bombesin sequence should provide safe working conditions for further development of this class of drug delivery vehicles.

  12. Biocompatible Soft Nanoparticles with Multiple Morphologies Obtained from Nanoprecipitation of Amphiphilic Graft Copolymers in a Backbone-Selective Solvent.

    Science.gov (United States)

    Le Fer, Gaëlle; Le Cœur, Clémence; Guigner, Jean-Michel; Amiel, Catherine; Volet, Gisèle

    2017-03-21

    Stealth nanocarriers are a promising technology for the treatment of diseases. However, the preparation and characterization of well-defined soft nanoparticulate systems remain challenging. Here we describe a platform of amphiphilic graft copolymers leading to nanoparticles with multiple morphologies and the role of the hydrophilic backbone in their interaction with a model protein. The amphiphilic graft copolymers platform was composed of hydrophilic backbone poly(2-methyl-2-oxazoline-co-2-pentyl-2-oxazoline) (P(MeOx-co-PentOx)), prepared via cationic ring-opening polymerization. Hydrophobic poly(d,l-lactide) (PLA) chains were grafted on the backbone via Huisgen 1,3-dipolar cycloaddition. The "click" copper-catalyzed cycloaddition reactions of azides with alkynes (CuAAC) were successfully carried out, and a series of amphiphilic copolymers were prepared containing a backbone with a number-average molecular weight of 14.2 × 10 3 g mol -1 and different hydrophobic PLA grafts with various molecular weights (2.8 × 10 3 -12.4 × 10 3 g mol -1 ). These original architectures of copolymers, when nanoprecipitated in water, the backbone-selective solvent, allowed us to obtain various structures of nanoparticles with a hydrodynamic diameter in the range of 65-99 nm. More interestingly, a plurality of morphologies going from unilamellar, multilamellar, and large compound vesicles to core-shell nanoparticles and depending on the PLA molecular weights were evidenced by combining cryo-transmission electron microscopy (cryo-TEM) and small-angle neutron scattering (SANS) studies. A first evaluation of their stealthiness by studying the stability and the interaction of these nano-objects with a model protein revealed the role played by the P(MeOx-co-PentOx) in these interactions, demonstrating the utility of this amphiphilic graft copolymers platform with well-defined architectures for the design of nanocarriers in drug delivery applications.

  13. New amphiphilic glycopolypeptide conjugate capable of self-assembly in water into reduction-sensitive micelles for triggered drug release

    International Nuclear Information System (INIS)

    Yang, Hui-Kang; Zhang, Li-Ming

    2014-01-01

    For the development of biomimetic carriers for stimuli-sensitive delivery of anticancer drugs, a novel amphiphilic glycopolypeptide conjugate containing the disulfide bond was prepared for the first time by the ring-opening polymerization of benzyl glutamate N-carboxy anhydride in the presence of (propargyl carbamate)ethyl dithio ethylamine and then click conjugation with α-azido dextran. Its structure was characterized by Fourier-transform infrared spectroscopy and nuclear magnetic resonance analyses. Owing to its amphiphilic nature, such a conjugate could self assemble into nanosize micelles in aqueous medium, as confirmed by fluorometry, transmission electron microscopy and dynamic light scattering. For the resultant micelles, it was found to encapsulate poorly water-soluble anticancer drug (methotrexate, MTX) with the loading efficiency of 45.2%. By the in vitro drug release tests, the release rate of encapsulated MTX was observed to be accelerated significantly in the presence of 10 mM 1,4-dithio-DL-threitol (DTT), analogous to the intracellular redox potential. - Graphical abstract: New amphiphilic glycopolypeptide conjugate containing the disulfide bond could self-assemble in aqueous solution into reduction-sensitive micelles for triggered release of an anticancer drug (methotrexate, MTX) in the presence of 10 mM 1,4-dithio-DL-threitol (DTT). - Highlights: • Amphiphilic glycopolypeptide conjugate containing disulfide bond was prepared. • Such a conjugate self assembled in aqueous solution into nanosize micelles. • The resultant micelles could encapsulate effectively methotrexate drug. • The drug-loaded micelles showed a reduction-sensitive drug release behavior

  14. One-Pot Synthesis of (+)-Nootkatone via Dark Singlet Oxygenation of Valencene: The Triple Role of the Amphiphilic Molybdate Catalyst

    OpenAIRE

    Bing Hong; Raphaël Lebeuf; Stéphanie Delbaere; Paul L. Alsters; Véronique Nardello-Rataj

    2016-01-01

    Efficient one-pot catalytic synthesis of (+)-nootkatone was performed from (+)-valencene using only hydrogen peroxide and amphiphilic molybdate ions. The process required no solvent and proceeded in three cascade reactions: (i) singlet oxygenation of valencene according to the ene reaction; (ii) Schenck rearrangement of one hydroperoxide into the secondary β-hydroperoxide; and (iii) dehydration of the hydroperoxide into the desired (+)-nootkatone. The solvent effect on the hydroperoxide rearr...

  15. Administration of a dipeptidyl peptidase IV inhibitor enhances the intestinal adaptation in a mouse model of short bowel syndrome

    DEFF Research Database (Denmark)

    Okawada, Manabu; Holst, Jens Juul; Teitelbaum, Daniel H

    2011-01-01

    Glucagon-like peptide-2 induces small intestine mucosal epithelial cell proliferation and may have benefit for patients who suffer from short bowel syndrome. However, glucagon-like peptide-2 is inactivated rapidly in vivo by dipeptidyl peptidase IV. Therefore, we hypothesized that selectively...... inhibiting dipeptidyl peptidase IV would prolong the circulating life of glucagon-like peptide-2 and lead to increased intestinal adaptation after development of short bowel syndrome....

  16. Self-Assembly of Amphiphilic Block Copolypeptoids with C 2 -C 5 Side Chains in Aqueous Solution

    KAUST Repository

    Fetsch, Corinna

    2014-12-22

    © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Nowadays, amphiphilic molecules play an important role in our life. In medical applications, amphiphilic block copolymers have attracted much attention as excipients in drug delivery systems. Here, the polymers are used as emulsifiers, micelles, or polymersomes with a hydrophilic corona block and a hydrophobic core or membrane. The aggregation behavior in aqueous solutions of a series of different amphiphilic block copolypeptoids comprising polysarcosine as a hydrophilic part is here reported. The formation of aggregates is investigated with 1H NMR spectroscopy and dynamic light scattering, and the determination of the critical micelle concentration (cmc) is performed using pyrene fluorescence spectroscopy. For the different block copolypeptoids cmc values ranging from 0.6 × 10-6 M to 0.1 × 10-3 M are found. The tendency to form micelles increases with increasing hydrophobicity at the nitrogen side chain in the hydrophobic moiety. Furthermore, in the case of the same hydrophobic side chain, a decreasing hydrophilic/lipophilic balance leads to the formation of larger aggregates. The aggregates formed in the buffer are able to solubilize the hydrophobic model compounds Reichardt\\'s dye and pyrene, and exhibit versatile microenvironments. Final investigations about the cytotoxicity reveal that the block copolypeptoids are well tolerated by mammalian cells up to high concentrations.

  17. Host-Guest Interaction between Corona[n]arene and Bisquaternary Ammonium Derivatives for Fabricating Supra-Amphiphile.

    Science.gov (United States)

    Zeng, Lingda; Guo, Qing-Hui; Feng, Yuanning; Xu, Jiang-Fei; Wei, Yuhan; Li, Zhibo; Wang, Mei-Xiang; Zhang, Xi

    2017-06-13

    The interactions between a host, water-soluble corona[n]arene (S6-CAP), and a series of guests, bisquaternary ammonium derivatives (CnDAs), in water, were investigated. The host and guest can form 1:1 host-guest complex. Their binding constants decrease as the alkyl length of CnDAs increases, which can be tunable ranging from 10 3 to 10 6 M -1 . The binding processes are mainly entropy-driven, while the enthalpy changes also play an important role in enhancing the host-guest interactions. In addition, a supra-amphiphile was fabricated with S6-CAP and a normal surfactant bearing bisquaternary ammonium (C4R). The S6-CAP·C4R complex forms micellar aggregates in water, and the system possesses better assembling activity and dilution stability than its building block C4R. This study enriches the families of supra-amphiphiles with a new architecture, and employing such a supra-amphiphile in biofunctional materials is highly anticipated.

  18. Novel amphiphilic poly(dimethylsiloxane) based polyurethane networks tethered with carboxybetaine and their combined antibacterial and anti-adhesive property

    Science.gov (United States)

    Jiang, Jingxian; Fu, Yuchen; Zhang, Qinghua; Zhan, Xiaoli; Chen, Fengqiu

    2017-08-01

    The traditional nonfouling materials are powerless against bacterial cells attachment, while the hydrophobic bactericidal surfaces always suffer from nonspecific protein adsorption and dead bacterial cells accumulation. Here, amphiphilic polyurethane (PU) networks modified with poly(dimethylsiloxane) (PDMS) and cationic carboxybetaine diol through simple crosslinking reaction were developed, which had an antibacterial efficiency of 97.7%. Thereafter, the hydrolysis of carboxybetaine ester into zwitterionic groups brought about anti-adhesive properties against bacteria and proteins. The surface chemical composition and wettability performance of the PU network surfaces were investigated by attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS) and contact angle analysis. The surface distribution of PDMS and zwitterionic segments produced an obvious amphiphilic heterogeneous surface, which was demonstrated by atomic force microscopy (AFM). Enzyme-linked immunosorbent assays (ELISA) were used to test the nonspecific protein adsorption behaviors. With the advantages of the transition from excellent bactericidal performance to anti-adhesion and the combination of fouling resistance and fouling release property, the designed PDMS-based amphiphilic PU network shows great application potential in biomedical devices and marine facilities.

  19. Adsorption of poly(ethylene oxide)-containing amphiphilic polymers on solid-liquid interfaces: Fundamentals and applications.

    Science.gov (United States)

    Bodratti, Andrew M; Sarkar, Biswajit; Alexandridis, Paschalis

    2017-06-01

    The adsorption of amphiphilic molecules of varying size on solid-liquid interfaces modulates the properties of colloidal systems. Nonionic, poly(ethylene oxide) (PEO)-based amphiphilic molecules are particularly useful because of their graded hydrophobic-hydrophilic nature, which allows for adsorption on a wide array of solid surfaces. Their adsorption also results in other useful properties, such as responsiveness to external stimuli and solubilization of hydrophobic compounds. This review focuses on the adsorption properties of PEO-based amphiphiles, beginning with a discussion of fundamental concepts pertaining to the adsorption of macromolecules on solid-liquid interfaces, and more specifically the adsorption of PEO homopolymers. The main portion of the review highlights studies on factors affecting the adsorption and surface self-assembly of PEO-PPO-PEO block copolymers, where PPO is poly(propylene oxide). Block copolymers of this type are commercially available and of interest in several fields, due to their low toxicity and compatibility in aqueous systems. Examples of applications relevant to the interfacial behavior of PEO-PPO-PEO block copolymers are paints and coatings, detergents, filtration, and drug delivery. The methods discussed herein for manipulating the adsorption properties of PEO-PPO-PEO are emphasized for their ability to shed light on molecular interactions at interfaces. Knowledge of these interactions guides the formulation of novel materials with useful mesoscale organization and micro- and macrophase properties. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Compartmentalization Technologies via Self-Assembly and Cross-Linking of Amphiphilic Random Block Copolymers in Water.

    Science.gov (United States)

    Matsumoto, Mayuko; Terashima, Takaya; Matsumoto, Kazuma; Takenaka, Mikihito; Sawamoto, Mitsuo

    2017-05-31

    Orthogonal self-assembly and intramolecular cross-linking of amphiphilic random block copolymers in water afforded an approach to tailor-make well-defined compartments and domains in single polymer chains and nanoaggregates. For a double compartment single-chain polymer, an amphiphilic random block copolymer bearing hydrophilic poly(ethylene glycol) (PEG) and hydrophobic dodecyl, benzyl, and olefin pendants was synthesized by living radical polymerization (LRP) and postfunctionalization; the dodecyl and benzyl units were incorporated into the different block segments, whereas PEG pendants were statistically attached along a chain. The copolymer self-folded via the orthogonal self-assembly of hydrophobic dodecyl and benzyl pendants in water, followed by intramolecular cross-linking, to form a single-chain polymer carrying double yet distinct hydrophobic nanocompartments. A single-chain cross-linked polymer with a chlorine terminal served as a globular macroinitiator for LRP to provide an amphiphilic tadpole macromolecule comprising a hydrophilic nanoparticle and a hydrophobic polymer tail; the tadpole thus self-assembled into multicompartment aggregates in water.