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Sample records for amphiphilic short peptides

  1. 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

  2. Self-Assembly and Hydrogelation of Peptide Amphiphiles

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    Wahyudi Priyono Suwarso

    2012-04-01

    Full Text Available Seven peptide amphiphiles were successfully synthesized using solid phase peptide synthesis method. Peptide amphiphiles were characterized using matrix assisted laser desorption/ionization (MALDI. Atomic force microscopy (AFM study showed that peptide amphiphiles having glycine, valine, or proline as linker, self-assembled into 100-200 nm nanofibers structure. According to our research, both peptide amphiphile with positive and negative charges bear similar self-assembly properties. Peptide amphiphile also showed its capability as low molecular weight gelator (LMWG. Peptide amphiphiles bearing C-16 and C-12 as alkyl showed better hydrogelation properties than C-8 alkyl. Five out of seven peptide amphiphiles have minimum gelation concentration (MGC lower than 1% (w/v.

  3. Peptide Amphiphiles in Corneal Tissue Engineering

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    Martina Miotto

    2015-08-01

    Full Text Available The increasing interest in effort towards creating alternative therapies have led to exciting breakthroughs in the attempt to bio-fabricate and engineer live tissues. This has been particularly evident in the development of new approaches applied to reconstruct corneal tissue. The need for tissue-engineered corneas is largely a response to the shortage of donor tissue and the lack of suitable alternative biological scaffolds preventing the treatment of millions of blind people worldwide. This review is focused on recent developments in corneal tissue engineering, specifically on the use of self-assembling peptide amphiphiles for this purpose. Recently, peptide amphiphiles have generated great interest as therapeutic molecules, both in vitro and in vivo. Here we introduce this rapidly developing field, and examine innovative applications of peptide amphiphiles to create natural bio-prosthetic corneal tissue in vitro. The advantages of peptide amphiphiles over other biomaterials, namely their wide range of functions and applications, versatility, and transferability are also discussed to better understand how these fascinating molecules can help solve current challenges in corneal regeneration.

  4. Rational design of purely peptidic amphiphiles for drug delivery applications

    OpenAIRE

    Bruyn Ouboter, Dirk de

    2011-01-01

    A broad range of new properties is emerging from supramolecular aggregates. Self-assembled structures of purely peptidic amphiphiles exploit these properties to produce biocompatible, biodegradable, smart materials for drug administration. This thesis explores the design, synthesis, purification, characterization of purely peptidic amphiphiles, and evaluates potential applications. The first chapter provides a general introduction to the field of self-assembly, and of drug delivery as com...

  5. Design of nanostructures based on aromatic peptide amphiphiles.

    Science.gov (United States)

    Fleming, Scott; Ulijn, Rein V

    2014-12-01

    Aromatic peptide amphiphiles are gaining popularity as building blocks for the bottom-up fabrication of nanomaterials, including gels. These materials combine the simplicity of small molecules with the versatility of peptides, with a range of applications proposed in biomedicine, nanotechnology, food science, cosmetics, etc. Despite their simplicity, a wide range of self-assembly behaviours have been described. Due to varying conditions and protocols used, care should be taken when attempting to directly compare results from the literature. In this review, we rationalise the structural features which govern the self-assembly of aromatic peptide amphiphiles by focusing on four segments, (i) the N-terminal aromatic component, (ii) linker segment, (iii) peptide sequence, and (iv) C-terminus. It is clear that the molecular structure of these components significantly influences the self-assembly process and resultant supramolecular architectures. A number of modes of assembly have been proposed, including parallel, antiparallel, and interlocked antiparallel stacking conformations. In addition, the co-assembly arrangements of aromatic peptide amphiphiles are reviewed. Overall, this review elucidates the structural trends and design rules that underpin the field of aromatic peptide amphiphile assembly, paving the way to a more rational design of nanomaterials based on aromatic peptide amphiphiles. PMID:25199102

  6. Tuning peptide amphiphile supramolecular structure for biomedical applications

    Science.gov (United States)

    Pashuck, Eugene Thomas, III

    The use of biomaterials in regenerative medicine has been an active area of research for more than a decade. Peptide amphiphiles, which are short peptide sequences coupled to alkyl tails, have been studied in the Stupp group since the beginning of the decade and been used for a variety of biomedical applications. Most of the work has focused on the bioactive epitopes places on the periphery of the PA molecules, but the interior amino acids, known as the beta-sheet region, give the PA nanofiber gel much of its mechanical strength. To study the important parameters in the beta-sheet region, six PA molecules were constructed to determine the influence of beta-sheet length and order of the amino acids in the beta-sheet. It was found that having beta-sheet forming amino acids near the center of the fiber improves PA gel stiffness, and that having extra amino acids that have preferences for other secondary structures, like alpha-helix decreased the gels stiffness. Using FTIR and circular dichroism it was found that the mechanical properties are influenced by the amount of twist in the beta-sheet, and PAs that have more twisted beta-sheets form weaker gels. The effect amino acid properties have on peptide amphiphile self-assembly where studied by synthesizining molecules with varying side group size and hydrophobicity. It was found that smaller amino acids lead to stiffer gels and when two amino acids had the same size the amino acid with the larger beta-sheet propensity lead to a stiffer gel. Furthermore, small changes in peptide structure were found to lead to big changes in nanostructure, as leucine and isoleucine, which have the same size but slightly different structures, form flat ribbons and cylindrical nanofibers, respectively. Phenylalanine and alanine were studied more indepth because they represent the effects of adding an aromatic group to amino acids in the beta-sheet regon. These phenylalanine PAs formed short, twisted ribbons when freshly dissolved in water

  7. Supramolecular chirality in self-assembled peptide amphiphile nanostructures.

    Science.gov (United States)

    Garifullin, Ruslan; Guler, Mustafa O

    2015-08-11

    Induced supramolecular chirality was investigated in the self-assembled peptide amphiphile (PA) nanosystems. Having shown that peptide chirality can be transferred to the covalently-attached achiral pyrene moiety upon PA self-assembly, the chiral information is transferred to molecular pyrene via weak noncovalent interactions. In the first design of a supramolecular chiral system, the chromophore was covalently attached to a peptide sequence (VVAGH) via an ε-aminohexanoic acid spacer. Covalent attachment yielded a PA molecule self-assembling into nanofibers. In the second design, the chromophore was encapsulated within the hydrophobic core of self-assembled nanofibers of another PA consisting of the same peptide sequence attached to lauric acid. We observed that supramolecular chirality was induced in the chromophore by PA assembly into chiral nanostructures, whether it was covalently attached, or noncovalently bound. PMID:26146021

  8. High Selective Performance of Designed Antibacterial and Anticancer Peptide Amphiphiles.

    Science.gov (United States)

    Chen, Cuixia; Chen, Yucan; Yang, Cheng; Zeng, Ping; Xu, Hai; Pan, Fang; Lu, Jian Ren

    2015-08-12

    Short designed peptide amphiphiles are attractive at killing bacteria and inhibiting cancer cell growth, and the flexibility in their structural design offers a great potential for improving their potency and biocompatibility to mammalian host cells. Amino acid sequences such as G(IIKK)nI-NH2 (n≥3) have been shown to be membrane lytic, but terminal amino acid modifications could impose a huge influence on their performance. We report in this work how terminal amino acid modifications to G(IIKK)3I-NH2 influence its α-helical structure, membrane penetrating ability, and selective actions against different cell types. Deletion of an N-terminal Gly or a C-terminal Ile did not affect their antibacterial activity much, an observation consistent with their binding behavior to negatively charged membrane lipid monolayers. However, the cytotoxicity against mammalian cells was much worsened by the N-terminal Gly deletion, consistent with an increase in its helical content. Despite little impact on the antibacterial activity of G(IIKK)3I-NH2, deletion of both terminal amino acids greatly reduced its antitumor activity. Cholesterol present in tumor cell membrane-mimic was thought to constrain (IIKK)3-NH2 from penetrating into the cancerous membranes, evident from its lowest surface physical activity at penetrating model lipid membranes. On the other hand, its low toxicity to normal mammalian cells and high antibacterial activity in vitro and in vivo made it an attractive antibacterial agent. Thus, terminal modifications can help rebalance the different interactions involved and are highly effective at manipulating their selective membrane responses.

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

    Science.gov (United States)

    Stupp, Samuel I.; Beniash, Elia; Hartgerink, Jeffrey D.

    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.

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

    Science.gov (United States)

    Stupp, Samuel I.; Beniash, Elia; Hartgerink, Jeffrey D.

    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.

  11. 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.

  12. Tissue Regeneration through Self-Assembled Peptide Amphiphile Nanofibers

    Directory of Open Access Journals (Sweden)

    Hossein Hosseinkhani

    2006-01-01

    Full Text Available Introduction: In the present study, we hypothesized that a novelapproach to promote vascularization would be to create injectablethree dimensional (3-D scaffolds within growth factor that enhancethe sustained release of growth factor and induce the angiogenesis.Material and Methods: We demonstrate that a 3-D scaffold can beformed by mixing of peptide-amphiphile (PA aqueous solution withhepatocyte growth factor (HGF solution. PA was synthesized bystandard solid phase chemistry that ends with the alkylation of theNH2 terminus of the peptide. The sequence of arginine-glycineasparticacid (RGD was included in peptide design as well. A 3-Dnetwork of nanofibers was formed by mixing HGF suspensions withdilute aqueous solution of PA.Results: Scanning electron microscopy (SEM examination revealedthe formation of fibrous assemblies with an extremely high aspectratio and high surface areas with mean diameter of less than 200 nm.In vitro HGF release profile of 3-D nanofibers was investigated whileangiogenesis induced by the released HGF was being assessed. Invivo potential ability of PA nanofibers to induce angiogenesis wasassessed through subcutaneous injection of PA solution, HGFsolution, and PA in combination with HGF solutions. Injection of PAwith HGF induced significant angiogenesis around the injected site,in marked contrast to HGF injection alone and PA injection alone.Conclusion: The combination of HGF-induced angiogenesis is apromising procedure to improve tissue regeneration.

  13. Tipping the scale from disorder to alpha-helix: Folding of amphiphilic peptides in the presence of macroscopic and molecular interfaces

    OpenAIRE

    Dalgıçdır, Cahit; Sayar, Mehmet; Globisch, Christoph; Peter, Christine

    2015-01-01

    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 ...

  14. 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

  15. Self-Assembling Peptide Amphiphiles for Targeted Drug Delivery

    Science.gov (United States)

    Moyer, Tyson

    The systemic delivery of therapeutics is currently limited by off-target side effects and poor drug uptake into the cells that need to be treated. One way to circumvent these issues is to target the delivery and release of therapeutics to the desired location while limiting systemic toxicity. Using self-assembling peptide amphiphiles (PAs), this work has investigated supramolecular nanostructures for the development of targeted therapies. Specifically, the research has focused on the interrelationships between presentation of targeting moeities and the control of nanostructure morphology in the context of systemic delivery for targeting cancer and vascular injuries. The self-assembly region of the PA was systematically altered to achieve control of nanostructure widths, from 100 nm to 10 nm, by the addition of valine-glutamic acid dimers into the chemical structure, subsequently increasing the degree of nanostructure twist. For the targeting of tumors, a homing PA was synthesized to include a dimeric, cyclic peptide sequence known to target the cancer-specific, death receptor 5 (DR5) and initiate apoptosis through the oligomerization of DR5. This PA presented a multivalent display of DR5-binding peptides, resulting in improved binding affinity measured by surface plasmon resonance. The DR5-targeting PA also showed enhanced efficacy in both in vitro and in vivo tumor models relative to non-targeted controls. Alternative modifications to the PA-based antitumor therapies included the use of a cytotoxic, membrane-lytic PA coassembled with a pegylated PA, which showed enhanced biodistribution and in vivo activity after coassembly. The functionalization of the hydrophobic core was also accomplished through the encapsulation of the chemotherapy camptothecin, which was shown to be an effective treatment in vivo. Additionally, a targeted PA nanostructure was designed to bind to the site of vascular intervention by targeting collagen IV. Following balloon angioplasty

  16. Self-assembling peptide amphiphile nanostructures for cancer therapy

    Science.gov (United States)

    Soukasene, Stephen

    The application of nanotechnology to cancer therapy shows great promise for reducing the burden of the disease. By virtue of their size, nanoscale objects preferentially accumulate in tumor tissue through an enhanced permeability and retention (EPR) effect. However, to fully overcome the issues that limit current cancer treatments, viable nanostructures must also impart multifunctionality and be fully compatible with their biological surrounds. The self-assembling peptide amphiphile (PA) materials studied extensively in the Stupp Research Group form very biocompatible high aspect ratio nanostructures that meet these criteria. This thesis investigates the development of PA nanostructures designed to treat cancer. We first look to use the PA as a drug delivery vehicle by entrapping a small hydrophobic anti-cancer drug, camptothecin, in the core of the nanostructures. Using a solvent evaporation technique to load the drug into the PA nanofibers, we are able to improve the aqueous solubility of the molecule by nearly 30-fold. TEM and AFM studies show that entrapment of drug molecules does not disrupt the self-assembled morphology of the nanofiber. In vitro and in vivo studies are also conducted to demonstrate the bioactivity of the drug after its entrapment. As a potential platform for novel therapeutics, we next develop techniques for using light irradiation to trigger self-assembly inside the confined space of liposomes. We encapsulate PA monomers that assemble under acidic conditions along with a photoacid generator inside liposomes. Upon exposure to 254 nm light, the PA monomers self assemble inside the liposome to form nanostructures, which we observe through a quick freeze/deep etch technique that allows us to look inside the liposomes by SEM and TEM. Last of all, the development and discovery of epitopes for targeting PA nanostructures to tumors are explored. Using phage display technology we generate two groups of peptide sequences, one of which can potentially

  17. Long-Circulating 15 nm Micelles Based on Amphiphilic 3-Helix Peptide-PEG Conjugates

    OpenAIRE

    Dong, He; Dube, Nikhil; Shu, Jessica Y.; Seo, Jai W.; Mahakian, Lisa M; Ferrara, Katherine W.; Xu, Ting

    2012-01-01

    Generating stable, multi-functional organic nanocarriers will have a significant impact on drug formulation. However, it remains a significant challenge to generate organic nanocarriers with a long circulation half-life, effective tumor penetration and efficient clearance of metabolites. We have advanced this goal by designing a new family of amphiphiles based on coiled-coil 3-helix bundle forming peptide-poly(ethylene glycol) conjugates. The amphiphiles self-assemble into monodisperse micell...

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

    Science.gov (United States)

    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

  19. Steps Towards the Formation of A Protocell: The Possible Role of Short Peptides

    Science.gov (United States)

    Fishkis, Maya

    2007-12-01

    The paper deals with molecular self-organization leading to formation of a protocell. Plausible steps towards a protocell include: polymerization of peptides and oligonucleotides on mineral surfaces; coevolution of peptides and oligonucleotides with formation of collectively autocatalytic sets; self-organization of short peptides into vesicles; entrapment of the peptide/oligonucleotide systems in mixed peptide and simple amphiphile membranes; and formation of functioning protocells with metabolism and cell division. The established propensity of short peptides to self-ordering and to formation of vesicles makes this sequence plausible. We further suggest that evolution of a protocell produced cellular ancestors of viruses as well as ancestors of cellular organisms.

  20. Self-assembly mechanisms of nanofibers from peptide amphiphiles in solution and on substrate surfaces

    Science.gov (United States)

    Liao, Hsien-Shun; Lin, Jing; Liu, Yang; Huang, Peng; Jin, Albert; Chen, Xiaoyuan

    2016-08-01

    We report the investigation of the self-assembly mechanism of nanofibers, using a small peptide amphiphile (NapFFKYp) as a model. Combining experimental and simulation methods, we identify the self-assembly pathways in the solution and on the substrates, respectively. In the solution, peptide amphiphiles undergo the nucleation process to grow into nanofibers. The nanofibers can further twist into high-ordered nanofibers with aging. On the substrates, peptide amphiphiles form nanofibers and nanosheet structures simultaneously. This surface-induced nanosheet consists of rod-like structures, and its thickness is substrate-dependent. Most intriguingly, water can transform the nanosheet into the nanofiber. Molecular dynamic simulation suggests that hydrophobic and ion-ion interactions are dominant forces during the self-assembly process.We report the investigation of the self-assembly mechanism of nanofibers, using a small peptide amphiphile (NapFFKYp) as a model. Combining experimental and simulation methods, we identify the self-assembly pathways in the solution and on the substrates, respectively. In the solution, peptide amphiphiles undergo the nucleation process to grow into nanofibers. The nanofibers can further twist into high-ordered nanofibers with aging. On the substrates, peptide amphiphiles form nanofibers and nanosheet structures simultaneously. This surface-induced nanosheet consists of rod-like structures, and its thickness is substrate-dependent. Most intriguingly, water can transform the nanosheet into the nanofiber. Molecular dynamic simulation suggests that hydrophobic and ion-ion interactions are dominant forces during the self-assembly process. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr04672j

  1. Biomimetic Self-Templated Hierarchical Structures of Collagen-Like Peptide Amphiphiles.

    Science.gov (United States)

    Jin, Hyo-Eon; Jang, Jaein; Chung, Jinhyo; Lee, Hee Jung; Wang, Eddie; Lee, Seung-Wuk; Chung, Woo-Jae

    2015-10-14

    Developing hierarchically structured biomaterials with tunable chemical and physical properties like those found in nature is critically important to regenerative medicine and studies on tissue morphogenesis. Despite advances in materials synthesis and assembly processes, our ability to control hierarchical assembly using fibrillar biomolecules remains limited. Here, we developed a bioinspired approach to create collagen-like materials through directed evolutionary screening and directed self-assembly. We first synthesized peptide amphiphiles by coupling phage display-identified collagen-like peptides to long-chain fatty acids. We then assembled the amphiphiles into diverse, hierarchically organized, nanofibrous structures using directed self-assembly based on liquid crystal flow and its controlled deposition. The resulting structures sustained and directed the growth of bone cells and hydroxyapatite biominerals. We believe these self-assembling collagen-like amphiphiles could prove useful in the structural design of tissue regenerating materials. PMID:26392232

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

    Science.gov (United States)

    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). PMID:26263446

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

    Science.gov (United States)

    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).

  4. Design of amphiphilic oligopeptides as models for fine tuning peptide assembly with plasmid DNA.

    Science.gov (United States)

    Goparaju, Geetha N; Gupta, Pardeep K

    2014-08-01

    We discuss the design of novel amphiphilic oligopeptides with hydrophobic and cationic amino acids to serve as models to understand peptide-DNA assembly. Biophysical and thermodynamic characterization of interaction of these amphiphilic peptides with plasmid DNA is presented. Peptides with at least +4 charges favor stable complex formation. Surface potential is dependent on the type of hydrophobic amino acid for a certain charge. Thermodynamically it is a spontaneous interaction between most of the peptides and plasmid DNA. Lys(7) and Tyr peptides with +4/+5 charges indicate cooperative binding with pDNA without saturation of interaction while Val(2)-Gly-Lys(4), Val-Gly-Lys(5), and Phe-Gly-Lys(5) lead to saturation of interaction indicating condensed pDNA within the range of N/Ps studied. We show that the biophysical properties of DNA-peptide complexes could be modulated by design and the peptides presented here could be used as building blocks for creating DNA-peptide complexes for various biomedical applications, mainly nucleic acid delivery.

  5. A designed amphiphilic peptide containing the silk fibroin motif as a potential carrier of hydrophobic drugs

    Institute of Scientific and Technical Information of China (English)

    Qinghan Zhou; Juan Lin; Jing Wang; Feng Li; Fushan Tang; Xiaojun Zhao

    2009-01-01

    The amphiphilic peptide is becoming attractive as a potential drug carder to improve the dissolvability of hydrophobic drugs in an aqueous system; thus, facilitating drug uptake by target cells. Here, we report a novel designed amphiphilic peptide, Ac-RADAGAGA-RADAGAGA-NH_2, which was able to stabilize pyrene, a hydrophobic model drug we chose to study in aqueous solution. This designed peptide formed a colloidal suspension by encapsulating pyrene inside the peptide-pyrene complex. Egg phosphatidylcholine (EPC) ves-icles were used to mimic cell bilayer membranes. We found that pyrene was released from the peptide coating into the EPC vesicles by mixing the colloidal suspension with EPC vesicles, which was followed by steady fluorescence spectra as a function of time. A calibration curve for the amount of pyrene released into the EPC vesicles at a given time was used to determine the final concentration of pyrene released into the lipid vesicles from the peptide-pyrene complex. The release rate of the peptide pyrene complex was calculated to quan-tify the transfer of pyrene into EPC vesicles.

  6. Super-resolution microscopy reveals structural diversity in molecular exchange among peptide amphiphile nanofibres

    Science.gov (United States)

    da Silva, Ricardo M. P.; van der Zwaag, Daan; Albertazzi, Lorenzo; Lee, Sungsoo S.; Meijer, E. W.; Stupp, Samuel I.

    2016-05-01

    The dynamic behaviour of supramolecular systems is an important dimension of their potential functions. Here, we report on the use of stochastic optical reconstruction microscopy to study the molecular exchange of peptide amphiphile nanofibres, supramolecular systems known to have important biomedical functions. Solutions of nanofibres labelled with different dyes (Cy3 and Cy5) were mixed, and the distribution of dyes inserting into initially single-colour nanofibres was quantified using correlative image analysis. Our observations are consistent with an exchange mechanism involving monomers or small clusters of molecules inserting randomly into a fibre. Different exchange rates are observed within the same fibre, suggesting that local cohesive structures exist on the basis of β-sheet discontinuous domains. The results reported here show that peptide amphiphile supramolecular systems can be dynamic and that their intermolecular interactions affect exchange patterns. This information can be used to generate useful aggregate morphologies for improved biomedical function.

  7. Extracellular matrix formation in self-assembled minimalistic bioactive hydrogels based on aromatic peptide amphiphiles

    OpenAIRE

    ZHOU, MI; Ulijn, Rein V.; Gough, Julie E

    2014-01-01

    The hitherto inconsistency in clinical performance for engineered skin drives the current development of novel cell-scaffolding materials; one challenge is to only extract essential characteristics from the complex native ECM (extracellular matrix) and incorporate them into a scaffold with minimal complexity to support normal cell functions. This study involved small-molecule-based bioactive hydrogels produced by the co-assembly of two aromatic peptide amphiphiles: Fmoc-FF (Fluorenylmethoxyca...

  8. Oligonucleotide delivery with cell surface binding and cell penetrating Peptide amphiphile nanospheres.

    Science.gov (United States)

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

    2015-05-01

    A drug delivery system designed specifically for oligonucleotide therapeutics can ameliorate the problems associated with the in vivo delivery of these molecules. The internalization of free oligonucleotides is challenging, and cytotoxicity is the main obstacle for current transfection vehicles. To develop nontoxic delivery vehicles for efficient transfection of oligonucleotides, we designed a self-assembling peptide amphiphile (PA) nanosphere delivery system decorated with cell penetrating peptides (CPPs) containing multiple arginine residues (R4 and R8), and a cell surface binding peptide (KRSR), and report the efficiency of this system in delivering G-3129, a Bcl-2 antisense oligonucleotide (AON). PA/AON (peptide amphiphile/antisense oligonucleotide) complexes were characterized with regards to their size and secondary structure, and their cellular internalization efficiencies were evaluated. The effect of the number of arginine residues on the cellular internalization was investigated by both flow cytometry and confocal imaging, and the results revealed that uptake efficiency improved as the number of arginines in the sequence increased. The combined effect of cell penetration and surface binding property on the cellular internalization and its uptake mechanism was also evaluated by mixing R8-PA and KRSR-PA. R8 and R8/KRSR decorated PAs were found to drastically increase the internalization of AONs compared to nonbioactive PA control. Overall, the KRSR-decorated self-assembled PA nanospheres were demonstrated to be noncytotoxic delivery vectors with high transfection rates and may serve as a promising delivery system for AONs. PMID:25828697

  9. Synthesis and In Vitro Evaluation of Amphiphilic Peptides and Their Nanostructured Conjugates

    Directory of Open Access Journals (Sweden)

    Samaneh Mohammadi

    2015-03-01

    Full Text Available Purpose: Breast cancer is the second leading cancer type among people of advanced countries. Various methods have been used for cancer treatment such as chemotherapy and radiotherapy. In the present study we have designed and synthesized a new group of drug delivery systems (DDS containing a new class of Cell Penetrating Peptides (CPPs named Peptide Amphiphiles (PAs. Methods: Two PAs and anionic peptides were synthesized using solid phase peptide synthesis (SPPS, namely [KW]4, [KW]5, E4 and E8. Then nano-peptides were synthesized by non-covalent binding between PAs and poly anions as [KW]4-E4, [KW]4-E8, [KW]5-E4 and [KW]5-E8. Results: Flow cytometry studies showed that increased chain length of PAs with a higher ratio between hydrophobicity and net charge results in increased intracellular uptake by MCF7 cells after 2h incubation. Moreover, nano-peptides showed greater intracellular uptake compared to PAs. Anti-proliferative assay revealed that by increasing chain length of PAs, the toxicity effect on MCF7 cells is reduced, however nano-peptides did not show significant toxicity on MCF7 cells even at high concentration levels. Conclusion: These data suggest that due to the lack of toxicity effect at high concentration levels and also high cellular uptake, nano-peptides are more suitable carrier compared to PAs for drug delivery.

  10. 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 ...

  11. Peptide-based gemini amphiphiles: phase behavior and rheology of wormlike micelles.

    Science.gov (United States)

    Shrestha, Rekha Goswami; Nomura, Kazuyuki; Yamamoto, Masashi; Yamawaki, Yukio; Tamura, Yoshinaga; Sakai, Kenichi; Sakamoto, Kazutami; Sakai, Hideki; Abe, Masahiko

    2012-11-01

    Aqueous binary phase behavior of a peptide-based gemini amphiphile with glutamic acid and lysine as spacer group, acylglutamyllysilacylglutamate (m-GLG-m where m = 12, 14, and 16), has been reported over a wide range of concentration and temperature. Lauroylglutamyllysillauroylglutamate, 12-GLG-12, self-assembles into spherical micelles above critical micelle concentration (CMC). The micellar region extends up to 32 wt %, and an ordering of spherical micelles into micellar cubic phase, I(1), takes place at 33 wt % at 25 °C. The phase transition, I(1) - hexagonal liquid crystal, (H(1)) - lamellar liquid crystal, (L(α)) has been observed with further increase in concentration; moreover, mixed phases are also observed between the pure liquid crystal domains. Similar phases were observed with 16-GLG-16 above 50 °C (Krafft temperature). The partial ternary phase behavior shows that the micellar solutions of m-GLG-m can solubilize a large amount of cationic amphiphile, alkyltrimethylammonium bromide, C(n)TAB, (where n = 14 (TTAB) and 16 (CTAB)) at 25 °C. An addition of C(n)TAB to the aqueous solutions of 16-GLG-16 in a dilute region forms a transparent solution of viscoelastic wormlike micelles at very low concentration (0.25 wt %) even at ambient condition. A mixture of oppositely charged amphiphiles, m-GLG-m and C(n)TAB, exhibits synergism as a result the amphiphile layer curvature, becomes less positive, and favors the transition from sphere to rod to transient networks (wormlike micelles). The gemini amphiphile, 16-GLG-16, forms wormlike micelles at relatively low concentrations compared to others reported so far. Viscosity increases by six orders of magnitude compared to that of pure solvent. The hydrophobic chain length of m-GLG-m and coamphiphile affects the rheology; the maximum viscosity achieved with 16-GLG-16/H(2)O/CTAB is higher than that of 14-GLG-14/H(2)O/CTAB, 12-GLG-12/H(2)O/CTAB, and 16-GLG-16/H(2)O/TTAB systems. These temperature-sensitive systems

  12. Structural transformation of peptide amphiphile self-assembly induced by headgroup charge and size regulation

    Science.gov (United States)

    Gao, Changrui; Bedzyk, Michael; Olvera, Monica; Kewalramani, Sumit; Palmer, Liam

    The ability to control the nano and the meso-scale architecture of molecular assemblies is one of the major challenges in nanoscience. Significantly, structural transformations of amphiphilic aggregates induced by variations in environmental conditions have attracted attention due to their biotechnological relevance. Here, we study the assembly in aqueous solution for a modular series of peptide amphiphiles with 3, 2 or 1 lysine groups conjugated to a C16 carbon tail (C16K3, C16K2 and C16K1) . This system design allow us to probe how the equilibrium structure of the self-assembly can be tuned by controlling the coupling between steric (via choice of headgroup: K3, K2, or K1) and electrostatic (via solution pH) interactions. Solution small- and wide-angle X-ray scattering (SAXS/WAXS) and transmission electron microscopy (TEM) studies reveal that depending on pH and number of lysines in the lipid headgroup, amphiphiles can assemble into a range of structures: spherical micelles, bilayer ribbons and vesicles. We also perform detailed phase space mapping of pH-and headgroup size dependency of the structures of assembly over 0.1-100 nm length scales via SAXS/WAXS. The experimental results in conjunction with molecular dynamics (MD) simulations deduce quantitative relations between pH-dependent molecular charges, steric constraints and self-assembly morphologies, which is significant for developing experimental routes to obtain assembly structures with specific nano- and meso-scale features through controlled external stimuli.

  13. Formation of size-controlled, denaturation-resistant lipid nanodiscs by an amphiphilic self-polymerizing peptide.

    Science.gov (United States)

    Kondo, Hiroaki; Ikeda, Keisuke; Nakano, Minoru

    2016-10-01

    Nanodiscs are discoidal particles with a planar phospholipid bilayer enwrapped by proteins such as apolipoprotein A-I. Nanodiscs have been widely used for analyzing structures and functions of membrane proteins by dispersing them in solution. They are expected to be used as drug carriers and therapeutic agents. Amphiphilic peptides are known to form nanodiscs. However, the lipid-peptide nanodiscs are relatively unstable in solution, making them unsuitable for many applications. Here, we report the synthesis of an amphiphilic self-polymerizing peptide termed ASPP1, which polymerizes by intermolecular native chemical ligation reactions. ASPP1 spontaneously formed nanodiscs when added to phospholipid vesicles without using detergents. The diameter of the planar lipid bilayer in the nanodiscs was controlled by the lipid:peptide molar ratio. ASPP1-nanodiscs exhibited greater stability at high temperatures or in the presence of urea than nanodiscs formed by the non-polymerizing amphiphilic peptide or apolipoprotein A-I. Average and maximal degrees of ASPP1 polymerization were 2.4 and 12, respectively. Self-polymerization of the peptide appears to be responsible for stabilization of the nanodiscs. Our results open a new avenue for the development of nanodisc technology. PMID:27393815

  14. Salt-resistant short antimicrobial peptides.

    Science.gov (United States)

    Mohanram, Harini; Bhattacharjya, Surajit

    2016-05-01

    Antimicrobial peptides (AMPs) are promising leads for the development of antibiotics against drug resistant bacterial pathogens. However, in vivo applications of AMPs remain obscure due to salt and serum mediated inactivation. The high cost of chemical synthesis of AMPs also impedes potential clinical application. Consequently, short AMPs resistant toward salt and serum inactivation are desirable for the development of peptide antibiotics. In this work, we designed a 12-residue amphipathic helical peptide RR12 (R-R-L-I-R-L-I-L-R-L-L-R-amide) and two Trp containing analogs of RR12 namely RR12Wpolar (R-R-L-I-W-L-I-L-R-L-L-R-amide), and RR12Whydro (R-R-L-I-R-L-W-L-R-L-L-R-amide). Designed peptides demonstrated potent antibacterial activity; MIC ranging from 2 to 8 μM, in the presence of sodium chloride (150 mM and 300 mM). Antibacterial activity of these peptides was also detected in the presence of human serum. Designed peptides, in particular RR12 and RR12Whydro, were only poorly hemolytic. As a mode of action; these peptides demonstrated efficient permeabilization of bacterial cell membrane and lysis of cell structure. We further investigated interactions of the designed peptides with lipopolysaccharide (LPS), the major component of the outer membrane permeability barrier of Gram-negative bacteria. Designed peptides adopted helical conformations in complex with LPS. Binding of peptides with LPS has yielded dissociation the aggregated structures of LPS. Collectively, these designed peptides hold ability to be developed for salt-resistant antimicrobial compounds. Most importantly, current work provides insights for designing salt-resistant antimicrobial peptides. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 345-356, 2016. PMID:26849911

  15. Molecular dynamics simulation of {beta}-sheet formation in self-assembled peptide amphiphile fibers

    Energy Technology Data Exchange (ETDEWEB)

    Lee, One-Sun; Liu Yamei; Schatz, George C., E-mail: schatz@chem.northwestern.edu [Northwestern University, Department of Chemistry (United States)

    2012-08-15

    The influence of amino acid sequence on the secondary structure of peptide amphiphile (PAs) cylindrical micelles and fibers that are self-assembled in solution is studied using molecular dynamics simulations. Simulations for two choices of PAs were performed, starting with structures that have the correct overall shape, but which restructure considerably during the simulation, with one fiber being composed of valine rich PAs and the other of alanine rich PAs. Self-assembly is similar in both simulations, with stable fibers (diameter is 7.7-8 nm) obtained after 40 ns. We find that the valine rich PA fiber has a higher {beta}-sheet population than the alanine rich fiber, and that the number of hydrogen bonds is higher. This behavior of the valine rich fiber is consistent with experimental measurements of higher stiffness, and it shows that stiffness can be varied while still maintaining self-assembly.

  16. Cytocompatibility of Self-assembled Hydrogel from IKVAV-containing Peptide Amphiphile with Neural Stem Cells

    Institute of Scientific and Technical Information of China (English)

    SONG Yulin; ZHENG Qixin; GUO Xiaodong; ZHENG Jianfeng

    2009-01-01

    Neural Stem Cells(NSCs)were incubated with self-assembled hydrogel from IKVAV-containing peptide amphiphile(IKVAV-PA)for one week.The cytocompatibility of hydrogel was evaluated.NSCs were seeded in three-dimensional(3D)hydrogels(Experimental Group,EG)or surface of coverslips(Control Group,CG),double-labeled with Calcein-AM and PI.A growth curve of cells was obtained according to CCK-8.TEM study of hydrogel revealed a network of nanofibers. NSCs began to proliferate after 24 h of incubation,and formed bigger neurospheres at 48 h in EG than in CG.Cell proliferation activity was higher in EG than in CG(P<0.05).The self-assembled Hydrogel had good cytocompatibility and promoted the proliferation of NSCs.

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

    OpenAIRE

    Cahit Dalgicdir; Christoph Globisch; Christine Peter; Mehmet Sayar

    2015-01-01

    RESEARCH ARTICLE Tipping the Scale from Disorder to Alpha-helix: Folding of Amphiphilic Peptides in the Presence of Macroscopic and Molecular Interfaces Cahit Dalgicdir1, Christoph Globisch2, Christine Peter2*, Mehmet Sayar1* 1 College of Engineering, Koç University, Istanbul, Turkey, 2 Theoretical Chemistry, University of Konstanz, Konstanz, Germany * (CP); (MS) Abstract Secondary amphiphilicity is inherent to the...

  18. 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

  19. Heparin-binding peptide amphiphile supramolecular architectures as platforms for angiogenesis and drug delivery

    Science.gov (United States)

    Chow, Lesleyann W.

    A fascinating phenomenon in nature is the self-assembly of molecules into a functional, hierarchical structure. In the past decade, the Stupp Laboratory has developed several classes of self-assembling biomaterials, one of which is the synthetic peptide amphiphile (PA). Self-assembling PAs are attractive and versatile biomolecules that can be customized for specific applications in regenerative medicine. In particular, a heparin-binding peptide amphiphile (HBPA) containing a specific heparin-binding peptide sequence was used here to induce angiogenesis and serve as a delivery vehicle for growth factors and small hydrophobic molecules. Throughout this dissertation, the HBPA/heparin system is used in different architectures for a variety of regenerative medicine applications. In one aspect of this work, hybrid scaffolds made from HBPA/heparin gelled on a poly(L-lactic acid) (PLLA) fiber mesh were used to promote angiogenesis to facilitate pancreatic islet transplantation for the treatment of type 1 diabetes. Delivery of growth factors with HBPA/PLLA scafflolds increased vessel density in vivo and correlated with improved transplant outcomes in a streptozotocin-induced diabetic mouse model. Soluble HBPA nanofiber architectures were also useful for islet transplantation applications. These nanofibers were used at concentrations below gelation to deliver growth factors into the dense islet cell aggregate, promoting cell survival and angiogenesis in vitro. The nanostructures infiltrated the islets and promoted the retention of heparin and growth factors within the islet. Another interesting growth factor release system discussed here is the HBPA membrane structure. HBPA was found to self-assemble with hyaluronic acid, a large biopolymer found in the body, into macroscopic, hierarchically-ordered membranes. Heparin was incorporated into these membranes and affected the membrane's mechanical properties and growth factor release. Human mesenchymal stem cells were also shown

  20. A redox-responsive mesoporous silica nanoparticle capped with amphiphilic peptides by self-assembly for cancer targeting drug delivery

    Science.gov (United States)

    Xiao, Dong; Jia, Hui-Zhen; Ma, Ning; Zhuo, Ren-Xi; Zhang, Xian-Zheng

    2015-05-01

    A redox-responsive mesoporous silica nanoparticle (RRMSN) was developed as a drug nanocarrier by noncovalent functionalization of MSNs with amphiphilic peptides containing the RGD ligand. The alkyl chain stearic acid (C18) with a thiol terminal group was anchored on the surface of MSNs via a disulfide bond, and the amphiphilic peptide (AP) C18-DSDSDSDSRGDS was coated by self-assembly through hydrophobic interactions between the octadecyl groups of MSNs and alkyl chains of AP, which played the role of a gatekeeper collectively. In vitro drug release profiles demonstrated that the anticancer drug (DOX) could be entrapped with nearly no leakage in the absence of dithiothreitol (DTT) or glutathione (GSH). With the addition of DTT or GSH, the entrapped drug released quickly due to the cleavage of the disulfide bond. It was found that after the internalization of MSNs by cancer cells via the receptor-mediated endocytosis, the surface amphiphilic peptides and alkyl chain of RRMSN/DOX were removed to induce rapid drug release intracellularly after the cleavage of the disulfide bond, triggered by GSH secreted in cancer cells. This novel intelligent RRMSN/DOX drug delivery system using self-assembly of amphiphilic peptides around the MSNs provides a facile, but effective strategy for the design and development of smart drug delivery for cancer therapy.A redox-responsive mesoporous silica nanoparticle (RRMSN) was developed as a drug nanocarrier by noncovalent functionalization of MSNs with amphiphilic peptides containing the RGD ligand. The alkyl chain stearic acid (C18) with a thiol terminal group was anchored on the surface of MSNs via a disulfide bond, and the amphiphilic peptide (AP) C18-DSDSDSDSRGDS was coated by self-assembly through hydrophobic interactions between the octadecyl groups of MSNs and alkyl chains of AP, which played the role of a gatekeeper collectively. In vitro drug release profiles demonstrated that the anticancer drug (DOX) could be entrapped with

  1. Purely peptidic amphiphiles : understanding and controlling their self-assembled structures

    OpenAIRE

    Schuster, Thomas Bernhard

    2011-01-01

    Amphiphilic molecules spontaneously self-assemble into a variety of structures in solution. The term amphiphilic indicates that one part of the molecule is attracted to the solvent, while the other is not. Interactions such as between solute-solvent and solute-solute thus determine the organization. Understanding the self-assembly means understanding those interactions and their driving forces. In the first chapter an overview of the self-organization of amphiphilic molecules into supermolecu...

  2. 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. PMID:26411438

  3. Extracellular matrix formation in self-assembled minimalistic bioactive hydrogels based on aromatic peptide amphiphiles.

    Science.gov (United States)

    Zhou, Mi; Ulijn, Rein V; Gough, Julie E

    2014-01-01

    The hitherto inconsistency in clinical performance for engineered skin drives the current development of novel cell-scaffolding materials; one challenge is to only extract essential characteristics from the complex native ECM (extracellular matrix) and incorporate them into a scaffold with minimal complexity to support normal cell functions. This study involved small-molecule-based bioactive hydrogels produced by the co-assembly of two aromatic peptide amphiphiles: Fmoc-FF (Fluorenylmethoxycarbonyl-diphenylalanine) and Fmoc-RGD (arginine-glycine-aspartic acid). Three-dimensionally cultured human dermal fibroblasts deposited dense ECM networks including fibronectin and collagen I within the hydrogels in a 14-day culture. The fibroblasts organized the fibrous ECM and contracted the gel without differentiating into myofibroblasts. The stiffness of the cell-gel constructs increased dramatically due to ECM formation and gel contraction. This created an economical biomimetic model-scaffold to further understand skin reconstruction in vitro and supplied a design pathway to create versatile cell-scaffolds with varied bioactivities and simplicity. PMID:24812581

  4. Self-Assembly of Peptide Amphiphiles Designed as Imaging Probes for 19F and Relaxation-Enhanced 1H imaging

    Science.gov (United States)

    Preslar, Adam Truett

    This work incorporates whole-body imaging functionality into peptide amphiphile (PA) nanostructures used for regenerative medicine to facilitate magnetic resonance imaging (MRI). Two strategies were employed: 1. Conjugation of gadolinium chelates to peptide nanostructures to monitor biomaterial degradation in vivo with MRI and inductively-coupled plasma-mass spectroscopy (ICP-MS) 2. Synthesis of perfluorinated moiety-bearing peptide amphiphiles for 19F-MRI. The Gd(III) chelate gadoteridol was conjugated by copper-catalyzed "click" chemistry to a series of PAs known to form cylindrical nanostructures. By fitting nuclear magnetic resonance dispersion (NMRD) profiles to the Solomon-Bloembergen-Morgan (SBM) equations, it was observed that the water exchange parameter (tauM) depended on thermal annealing or calcium ion cross-linking. The sequence C16V 3A3E3G(Gd) exhibited an acceleration of nearly 100 ns after thermal annealing and calcium addition. These gadolinium-labeled PAs were used to track in vivo degradation of gels within the tibialis anterior muscle in a murine model. The half-life of biomaterial degradation was determined to be 13.5 days by inductively coupled plasma mass spectrometry (ICP-MS) of Gd(III). Gel implants could be monitored by MRI for eight days before the signal dispersed due to implant degradation and dilution. Additionally, nanostructures incorporating highly fluorinated domains were investigated for use as MRI contrast agents. Short, perfluoroalkyane tails of seven or eight carbon atoms in length were grafted to PA sequences containing a V2A2 beta-sheet forming sequence. The V2A2 sequence is known to drive 1D nanostructure assembly. It was found that the sequences C7F13V2A 2E2 and C7F13V2A 2K3 formed 1D assemblies in water which transition from ribbon-like to cylindrical shape as pH increases from 4.5 to 8.0. Ribbon-like nanostructures had reduced magnetic resonance signal by T 2 relaxation quenching, whereas their cylindrical counterparts

  5. Immobilization of lipid vesicles on polymer support via an amphiphilic peptidic anchor: application to a membrane enzyme.

    Science.gov (United States)

    Percot, A; Zhu, X X; Lafleur, M

    2000-01-01

    To immobilize lipid vesicles on a polymer support, we have used a peptidic anchor with the following sequence: Ala-Ala-Leu-Leu-Leu-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-A la-Ala-Ala-Ala-Ala-Ala-Ala-Trp-Lys-Lys-Lys-Lys-Lys-Lys. This amphiphilic peptide was previously designed in our group to interact spontaneously and strongly with vesicles without perturbing their permeability. At the end of the solid-phase peptide synthesis, the peptide was left on the polymer beads and this novel polymer-peptide system was used for vesicle immobilization. It was shown that this polymer-peptide system could immobilize as much as 200 micromol of lipids per gram of dry resin. The amount of immobilized vesicles was decreased by a reduction of the proportion of the negatively charged lipids in the vesicles, indicating the importance of electrostatic interactions in the immobilization of the vesicles. The integrity of the vesicles was mostly preserved after the immobilization. This new polymer-peptide system was used easily and successfully to immobilize a membrane-bound enzyme, gamma-glutamyl transpeptidase. The activity of the membrane-bound enzyme was studied by monitoring the release of p-nitroaniline. The activity of the enzyme was still retained, even after being re-used eight times, indicating the strong immobilization of the enzyme in its active form. The polymer-peptide support could be regenerated by washing with ethanol and reused.

  6. 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.

  7. A hybrid biomimetic scaffold composed of electrospun polycaprolactone nanofibers and self-assembled peptide amphiphile nanofibers

    Energy Technology Data Exchange (ETDEWEB)

    Tambralli, Ajay; Blakeney, Bryan; Anderson, Joel; Kushwaha, Meenakshi; Andukuri, Adinarayana; Jun, Ho-Wook [Department of Biomedical Engineering, University of Alabama at Birmingham, 801 Shelby Building, 1825 University Boulevard, Birmingham, AL 35294 (United States); Dean, Derrick [Department of Materials Science and Engineering, University of Alabama at Birmingham, BEC 254, 1150 10th Ave South, Birmingham, AL 35294 (United States)], E-mail: hwjun@uab.edu

    2009-06-01

    Nanofibrous electrospun poly ({epsilon}-caprolactone) (ePCL) scaffolds have inherent structural advantages, but lack of bioactivity has limited their usefulness in biomedical applications. Thus, here we report the development of a hybrid, nanostructured, extracellular matrix (ECM) mimicking scaffold by a combination of ePCL nanofibers and self-assembled peptide amphiphile (PA) nanofibers. The PAs have ECM mimicking characteristics including a cell adhesive ligand (RGDS) and matrix metalloproteinase-2 (MMP-2) mediated degradable sites. Transmission electron microscope imaging verified successful PA self-assembly into nanofibers (diameters of 8-10 nm) using a solvent evaporation method. This evaporation method was then used to successfully coat PAs onto ePCL nanofibers (diameters of 300-400 nm), to develop hybrid, bioactive scaffolds. Scanning electron microscope characterization showed that the PA coatings did not interfere with the porous ePCL nanofiber network. Human mesenchymal stem cells (hMSCs) were seeded onto the hybrid scaffolds to evaluate their bioactivity. Significantly greater attachment and spreading of hMSCs were observed on ePCL nanofibers coated with PA-RGDS as compared to ePCL nanofibers coated with PA-S (no cell adhesive ligand) and uncoated ePCL nanofibers. Overall, this novel strategy presents a new solution to overcome the current bioactivity challenges of electrospun scaffolds and combines the unique characteristics of ePCL nanofibers and self-assembled PA nanofibers to provide an ECM mimicking environment. This has great potential to be applied to many different electrospun scaffolds for various biomedical applications.

  8. 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

  9. Water ordering controls the dynamic equilibrium of micelle-fibre formation in self-assembly of peptide amphiphiles

    Science.gov (United States)

    Deshmukh, Sanket A.; Solomon, Lee A.; Kamath, Ganesh; Fry, H. Christopher; Sankaranarayanan, Subramanian K. R. S.

    2016-08-01

    Understanding the role of water in governing the kinetics of the self-assembly processes of amphiphilic peptides remains elusive. Here, we use a multistage atomistic-coarse-grained approach, complemented by circular dichroism/infrared spectroscopy and dynamic light scattering experiments to highlight the dual nature of water in driving the self-assembly of peptide amphiphiles (PAs). We show computationally that water cage formation and breakage near the hydrophobic groups control the fusion dynamics and aggregation of PAs in the micellar stage. Simulations also suggest that enhanced structural ordering of vicinal water near the hydrophilic amino acids shifts the equilibrium towards the fibre phase and stimulates structure and order during the PA assembly into nanofibres. Experiments validate our simulation findings; the measured infrared O-H bond stretching frequency is reminiscent of an ice-like bond which suggests that the solvated water becomes increasingly ordered with time in the assembled peptide network, thus shedding light on the role of water in a self-assembly process.

  10. Co-adsorption of peptide amphiphile V(6)K and conventional surfactants SDS and C(12)TAB at the solid/water interface.

    Science.gov (United States)

    Jayawardane, Dharana; Pan, Fang; Lu, Jian R; Zhao, Xiubo

    2015-10-28

    Recent research has reported many attractive benefits from short peptide amphiphiles. A practical route for them to enter the real world of applications is through formulation with conventional surfactants. This study reports the co-adsorption of the surfactant-like peptide, V6K, with conventional anionic and cationic surfactants at the solid/water interface. The time-dependant adsorption behaviour was examined using spectroscopic ellipsometry whilst adsorbed layer composition and structural distribution of the components were investigated by neutron reflection with the use of hydrogen/deuterium labelling of the surfactant molecules. Both binary (surfactant/peptide mixtures) and sequential (peptide followed by surfactant) adsorption have been studied. It was found that at the hydrophilic SiO2/water interface, the peptide was able to form a stable, flat, defected bilayer structure however both the structure and adsorbed amount were highly dependent on the initial peptide concentration. This consequently affected surfactant adsorption. In the presence of a pre-adsorbed peptide layer anionic sodium dodecyl sulfate (SDS) could readily co-adsorb at the interface; however, cationic dodecyl trimethyl ammonium bromide (C12TAB) could not co-adsorb due to the same charge character. However on a trimethoxy octyl silane (C8) coated hydrophobic surface, V6K formed a monolayer, and subsequent exposure to cationic and anionic surfactants both led to some co-adsorption at the interface. In binary surfactant/peptide mixtures, it was found that adsorption was dependent on the molar ratio of the surfactant and peptide. For SDS mixtures below molar unity and concentrations below CMC for C12TAB, V6K was able to dominate adsorption at the interface. Above molar unity, no adsorption was detected for SDS/V6K mixtures. In contrast, C12TAB gradually replaced the peptide and became dominant at the interface. These results thus elucidate the adsorption behaviour of V6K, which was found to

  11. 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. PMID:27297498

  12. 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.

  13. Synthesis of Electroneutralized Amphiphilic Copolymers with Peptide Dendrons for Intramuscular Gene Delivery.

    Science.gov (United States)

    Pu, Linyu; Wang, Jiali; Li, Na; Chai, Qiuxia; Irache, Juan M; Wang, Gang; Tang, James Zhenggui; Gu, Zhongwei

    2016-06-01

    Intramuscular gene delivery materials are of great importance in plasmid-based gene therapy system, but there is limited information so far on how to design and synthesize them. A previous study showed that the peptide dendron-based triblock copolymer with its components arranged in a reversed biomembrane architecture could significantly increase intramuscular gene delivery and expression. Herein, we wonder whether copolymers with biomembrane-mimicking arrangement may have similar function on intramuscular gene delivery. Meanwhile, it is of great significance to uncover the influence of electric charge and molecular structure on the function of the copolymers. To address the issues, amphiphilic triblock copolymers arranged in hydrophilic-hydrophobic-hydrophilic structure were constructed despite the paradoxical characteristics and difficulties in synthesizing such hydrophilic but electroneutral molecules. The as-prepared two copolymers, dendronG2(l-lysine-OH)-poly propylene glycol2k(PPG2k)-dendronG2(l-lysine-OH) (rL2PL2) and dendronG3(l-lysine-OH)-PPG2k-dendronG3(l-lysine-OH) (rL3PL3), were in similar structure but had different hydrophilic components and surface charges, thus leading to different capabilities in gene delivery and expression in skeletal muscle. rL2PL2 was more efficient than Pluronic L64 and rL3PL3 when mediating luciferase, β-galactosidase, and fluorescent protein expressions. Furthermore, rL2PL2-mediated growth-hormone-releasing hormone expression could significantly induce mouse body weight increase in the first 21 days after injection. In addition, both rL2PL2 and rL3PL3 showed good in vivo biosafety in local and systemic administration. Altogether, rL2PL2-mediated gene expression in skeletal muscle exhibited applicable potential for gene therapy. The study revealed that the molecular structure and electric charge were critical factors governing the function of the copolymers for intramuscular gene delivery. It can be concluded that, combined

  14. Supra-molecular assembly of a lumican-derived peptide amphiphile enhances its collagen-stimulating activity.

    Science.gov (United States)

    Walter, Merlin N M; Dehsorkhi, Ashkan; Hamley, Ian W; Connon, Che J

    2016-02-01

    C16-YEALRVANEVTLN, a peptide amphiphile (PA) incorporating a biologically active amino acid sequence found in lumican, has been examined for its influence upon collagen synthesis by human corneal fibroblasts in vitro, and the roles of supra-molecular assembly and activin receptor-like kinase ALK receptor signaling in this effect were assessed. Cell viability was monitored using the Alamar blue assay, and collagen synthesis was assessed using Sirius red. The role of ALK signaling was studied by receptor inhibition. Cultured human corneal fibroblasts synthesized significantly greater amounts of collagen in the presence of the PA over both 7-day and 21-day periods. The aggregation of the PA to form nanotapes resulted in a notable enhancement in this activity, with an approximately two-fold increase in collagen production per cell. This increase was reduced by the addition of an ALK inhibitor. The data presented reveal a stimulatory effect upon collagen synthesis by the primary cells of the corneal stroma, and demonstrate a direct influence of supra-molecular assembly of the PA upon the cellular response observed. The effects of PA upon fibroblasts were dependent upon ALK receptor function. These findings elucidate the role of self-assembled nanostructures in the biological activity of peptide amphiphiles, and support the potential use of a self-assembling lumican derived PA as a novel biomaterial, intended to promote collagen deposition for wound repair and tissue engineering purposes. PMID:26626506

  15. Antimicrobial potential of lycosin-I, a cationic and amphiphilic peptide from the venom of the spider Lycosa singorensis.

    Science.gov (United States)

    Tan, H; Ding, X; Meng, S; Liu, C; Wang, H; Xia, L; Liu, Z; Liang, S

    2013-07-01

    Antimicrobial peptides (AMPs) are significant components of the innate immune system and play indispensable roles in the resistance to bacterial infection. Here, we investigated the antimicrobial activity of lycosin-I, a 24-residue cationic anticancer peptide derived from Lycosa singorensis with high structural similarity to several cationic and amphiphilic antimicrobial peptides. The antimicrobial activity of lycosin-I against 27 strains of microbes including bacteria and fungi was examined and compared with that of the Xenopus-derived AMP magainin 2 using a microdilution assay. Lycosin-I inhibited the growth of most microorganisms at low micromolar concentrations, and was a more potent inhibitor than magainin 2. Lycosin-I showed rapid, selective and broad-spectrum bactericidal activity and a synergistic effect with traditional antibiotics. In vivo, it showed potent bactericidal activity in a mouse thigh infection model. High Mg2+ concentrations reduced the antibacterial effect of lycosin-I, implying that the peptide might directly interact with the bacterial cell membrane. Uptake of the fluorogenic dye SYTOX and changes in the surface of lycosin-Itreated bacterial cells observed by scanning electron microscopy confirmed that lycosin-I permeabilized the cell membrane, resulting in the rapid bactericidal effect. Taken together, our findings indicate that lycosin-I is a promising peptide with the potential for the development of novel antibacterial agents.

  16. Self-Assembling Peptide Amphiphiles for Therapeutic Delivery of Proteins, Drugs, and Stem Cells

    Science.gov (United States)

    Lee, Sungsoo Seth

    Biomaterials are used to help regenerate or replace the structure and function of damaged tissues. In order to elicit desired therapeutic responses in vivo, biomaterials are often functionalized with bioactive agents, such as growth factors, small molecule drugs, or even stem cells. Therefore, the strategies used to incorporate these bioactive agents in the microstructures and nanostructures of biomaterials can strongly influence the their therapeutic efficacy. Using self-assembling peptide amphiphiles (PAs), this work has investigated supramolecular nanostructures with improved interaction with three types of therapeutic agents: bone morphogenetic protein 2 (BMP-2) which promotes osteogenic differentiation and bone growth, anti-inflammatory drug naproxen which is used to treat osteo- and rheumatoid arthritis, and neural stem cells that could differentiate into neurons to treat neurodegenerative diseases. For BMP-2 delivery, two specific systems were investigated with affinity for BMP-2: 1) heparin-binding nanofibers that display the natural ligand of the osteogenic protein, and 2) nanofibers that display a synthetic peptide ligand discovered in our laboratory through phage display to directly bind BMP-2. Both systems promoted enhanced osteoblast differentiation of pluripotent C2C12 cells and augmented bone regeneration in two in vivo models, a rat critical-size femur defect model and spinal arthrodesis model. The thesis also describes the use of PA nanofibers to improve the delivery of the anti-inflammatory drug naproxen. To promote a controlled release, naproxen was chemically conjugated to the nanofiber surface via an ester bond that would only be cleaved by esterases, which are enzymes found naturally in the body. In the absence of esterases, the naproxen remained conjugated to the nanofibers and was non-bioactive. On the other hand, in the presence of esterases, naproxen was slowly released and inhibited cyclooxygenase-2 (COX-2) activity, an enzyme responsible

  17. 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

  18. Ion-specific weak adsorption of salts and water/octanol transfer free energy of a model amphiphilic hexa-peptide

    International Nuclear Information System (INIS)

    An amphiphilic hexa-peptide has been used as a model to quantify how specific ion effects induced by addition of four salts tune the hydrophilic/hydrophobic balance and induce temperature-dependant coacervate formation from aqueous solution. The hexa-peptide chosen is present as a dimer with low transfer energy from water to octanol. Taking sodium chloride as the reference state in the Hofmeister scale, we identify water activity effects and therefore measure the free energy of transfer from water to octanol and separately the free energy associated to the adsorption of chaotropic ions or the desorption of kosmotropic ions for the same amphiphilic peptide. These effects have the same order of magnitude: therefore, both energies of solvation as well as transfer into octanol strongly depend on the nature of the electrolytes used to formulate any buffer. Model peptides could be used on separation processes based on criteria linked to 'Hofmeister' but different from volume and valency. (authors)

  19. Lysine-tagged peptide coupling onto polylactide nanoparticles coated with activated ester-based amphiphilic copolymer: a route to highly peptide-functionalized biodegradable carriers.

    Science.gov (United States)

    Handké, Nadège; Ficheux, Damien; Rollet, Marion; Delair, Thierry; Mabrouk, Kamel; Bertin, Denis; Gigmes, Didier; Verrier, Bernard; Trimaille, Thomas

    2013-03-01

    Efficient biomolecule conjugation to the surface of biodegradable colloidal carriers is crucial for their targeting efficiency in drug/vaccine delivery applications. We here propose a potent strategy to drastically improve peptide immobilization on biodegradable polylactide (PLA) nanoparticles (NPs). Our approach particularly relies on the use of an amphiphilic block copolymer PLA-b-poly(N-acryloxysuccinimide-co-N-vinylpyrrolidone) (PLA-b-P(NAS-co-NVP)) as NP surface modifier, whose the N-succinimidyl (NS) ester functions of the NAS units along the polymer chain ensure N-terminal amine peptide coupling. The well-known immunostimulatory peptide sequence derived from the human interleukin 1β (IL-1β), VQGEESNDK, was coupled on the NPs of 169 nm mean diameter in phosphate buffer (pH 8, 10 mM). A maximum amount of 2 mg immobilized per gram of NPs (i.e. 0.042 peptidenm(-2)) was obtained. Introduction of a three lysine tag at the peptide N-terminus (KKKVQGEESNDK) resulted in a dramatic improvement of the immobilized peptide amounts (27.5 mg/g NP, i.e. 0.417 peptidenm(-2)). As a comparison, the density of tagged peptide achievable on surfactant free PLA NPs of similar size (140 nm), through classical EDC or EDC/NHS activation of the surface PLA carboxylic end-groups, was found to be 6 mg/g NP (i.e. 0.075 peptidenm(-2)), showing the decisive impact of the P(NAS-co-NVP)-based hairy corona for high peptide coupling. These results demonstrate that combined use of lysine tag and PLA-b-P(NAS-co-NVP) surfactant represents a valuable platform to tune and optimize surface bio-functionalization of PLA-based biodegradable carriers. PMID:23277324

  20. Asymmetric catalysis with short-chain peptides.

    Science.gov (United States)

    Lewandowski, Bartosz; Wennemers, Helma

    2014-10-01

    Within this review article we describe recent developments in asymmetric catalysis with peptides. Numerous peptides have been established in the past two decades that catalyze a wide variety of transformations with high stereoselectivities and yields, as well as broad substrate scope. We highlight here catalytically active peptides, which have addressed challenges that had thus far remained elusive in asymmetric catalysis: enantioselective synthesis of atropoisomers and quaternary stereogenic centers, regioselective transformations of polyfunctional substrates, chemoselective transformations, catalysis in-flow and reactions in aqueous environments.

  1. Short peptides allowing preferential detection of Candida albicans hyphae.

    Science.gov (United States)

    Kaba, Hani E J; Pölderl, Antonia; Bilitewski, Ursula

    2015-09-01

    Whereas the detection of pathogens via recognition of surface structures by specific antibodies and various types of antibody mimics is frequently described, the applicability of short linear peptides as sensor molecules or diagnostic tools is less well-known. We selected peptides which were previously reported to bind to recombinant S. cerevisiae cells, expressing members of the C. albicans Agglutinin-Like-Sequence (ALS) cell wall protein family. We slightly modified amino acid sequences to evaluate peptide sequence properties influencing binding to C. albicans cells. Among the selected peptides, decamer peptides with an "AP"-N-terminus were superior to shorter peptides. The new decamer peptide FBP4 stained viable C. albicans cells more efficiently in their mature hyphal form than in their yeast form. Moreover, it allowed distinction of C. albicans from other related Candida spp. and could thus be the basis for the development of a useful tool for the diagnosis of invasive candidiasis.

  2. Amphiphilic Peptide Interactions with Complex Biological Membranes : Effect of peptide properties on antimicrobial and anti-inflammatory effects

    OpenAIRE

    Singh, Shalini

    2016-01-01

    With increasing problem of resistance development in bacteria against conventional antibiotics, as well as problems associated with diseases either triggered or enhanced by infection, there is an urgent need to identify new types of effective therapeutics for the treatment of infectious diseases and its consequences. Antimicrobial and anti-inflammatory peptides have attracted considerable interest as potential new antibiotics in this context. While antimicrobial function of such peptides is b...

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

    Directory of Open Access Journals (Sweden)

    Accardo A

    2014-05-01

    Full Text Available Antonella Accardo,1 Mariateresa Vitiello,2,3 Diego Tesauro,1 Marilena Galdiero,2 Emiliana Finamore,2 Francesca Martora,2 Rosalba Mansi,1 Paola Ringhieri,1 Giancarlo Morelli11Department of Pharmacy, Interuniversitary Centre for Research on Bioactive peptides, CIRPeB, University of Naples "Federico II", Institute of Biostructures and Bioimaging IBB-CNR, Naples, Italy; 2Department of Experimental Medicine, Section of Microbiology and Clinical Microbiology, Second University of Naples, Naples, Italy; 3Department of Clinical Pathology and Transfusion Medicine, University Hospital “Ruggi d'Aragona”, Salerno, ItalyAbstract: 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

  4. 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

    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...

  5. Transparent, conductive, and SERS-active Au nanofiber films assembled on an amphiphilic peptide template

    Science.gov (United States)

    Vinod, T. P.; Zarzhitsky, Shlomo; Morag, Ahiud; Zeiri, Leila; Levi-Kalisman, Yael; Rapaport, Hanna; Jelinek, Raz

    2013-10-01

    The use of biological materials as templates for functional molecular assemblies is an active research field at the interface between chemistry, biology, and materials science. We demonstrate the formation of gold nanofiber films on β-sheet peptide domains assembled at the air/water interface. The gold deposition scheme employed a recently discovered chemical process involving spontaneous crystallization and reduction of water-soluble Au(SCN)41- upon anchoring to surface-displayed amine moieties. Here we show that an interlinked network of crystalline Au nanofibers is readily formed upon incubation of the Au(iii) thiocyanate complex with the peptide monolayers. Intriguingly, the resultant films were optically transparent, enabled electrical conductivity, and displayed pronounced surface enhanced Raman spectroscopy (SERS) activity, making the approach a promising avenue for construction of nano-structured films exhibiting practical applications.The use of biological materials as templates for functional molecular assemblies is an active research field at the interface between chemistry, biology, and materials science. We demonstrate the formation of gold nanofiber films on β-sheet peptide domains assembled at the air/water interface. The gold deposition scheme employed a recently discovered chemical process involving spontaneous crystallization and reduction of water-soluble Au(SCN)41- upon anchoring to surface-displayed amine moieties. Here we show that an interlinked network of crystalline Au nanofibers is readily formed upon incubation of the Au(iii) thiocyanate complex with the peptide monolayers. Intriguingly, the resultant films were optically transparent, enabled electrical conductivity, and displayed pronounced surface enhanced Raman spectroscopy (SERS) activity, making the approach a promising avenue for construction of nano-structured films exhibiting practical applications. Electronic supplementary information (ESI) available: AFM analysis of the

  6. 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)

    Deuterium nuclear magnetic resonance (2H 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 ([2-2H]DOPS) or at the 11-position of the acyl chains ([11,11-2H2]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 [2-2H]DOPS and [11,11-2H2]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 Δvq values. When the peptide-lipid titrations are carried out without applying a freeze-thaw procedure to achieve full equilibration, two-component 2H 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. 2H 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

  7. 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

    Energy Technology Data Exchange (ETDEWEB)

    de Kroon, A.I.P.M.; Killian, J.A.; de Gier, J.; de Kruijff, B. (Univ. of Utrecht (Netherlands))

    1991-01-29

    Deuterium nuclear magnetic resonance ({sup 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 {beta}-position of the serine moiety ((2-{sup 2}H)DOPS) or at the 11-position of the acyl chains ((11,11-{sup 2}H{sub 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-{sup 2}H)DOPS and (11,11-{sup 2}H{sub 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){sub 100}, which were included for reasons of comparison, reveal increased {Delta}v{sub q} values. When the peptide-lipid titrations are carried out without applying a freeze-thaw procedure to achieve full equilibration, two-component {sup 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. {sup 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.

  8. Characterization and performance of short cationic antimicrobial peptide isomers.

    Science.gov (United States)

    Juba, Melanie; Porter, Devin; Dean, Scott; Gillmor, Susan; Bishop, Barney

    2013-07-01

    Cationic antimicrobial peptides (CAMPs) represent an ancient defense mechanism against invading bacteria, with peptides such as the cathelicidins being essential elements of vertebrate innate immunity. CAMPs are typically associated with broad-spectrum antimicrobial potency and limited bacterial resistance. The cathelicidin identified from the elapid snake Naja atra (NA-CATH) contains a semi-conserved repeated 11-residue motif (ATRA motif) with a sequence pattern consistent with formation of an amphipathic helical conformation. Short peptide amides (ATRA-1, -1A, -1P, and -2) generated based on the pair of ATRA motifs in NA-CATH exhibited varied antimicrobial potencies. The small size of the ATRA peptides, coupled with their varied antimicrobial performances, make them interesting models to study the impact various physico-chemical properties have on antimicrobial performance in helical CAMPs. Accordingly, the D- and L-enantiomers of the peptide ATRA-1A, which in earlier studies had shown both good antimicrobial performance and strong helical character, were investigated in order to assess the impact peptide stereochemistry has on antimicrobial performance and interaction with chiral membranes. The ATRA-1A isomers exhibit varied potencies against four bacterial strains, and their conformational properties in the presence of mixed zwitterionic/anionic liposomes are influenced by anionic lipid content. These studies reveal subtle differences in the properties of the peptide isomers. Differences are also seen in the abilities of the ATRA-1A isomers to induce liposome fusion/aggregation, bilayer rearrangement and lysing through turbidity studies and fluorescence microscopy. The similarities and differences in the properties of the ATRA-1A isomers could aid in efforts to develop D-peptide-based therapeutics using high-performing L-peptides as templates.

  9. Application of Collagen-Model Triple-Helical Peptide-Amphiphiles for CD44-Targeted Drug Delivery Systems

    Directory of Open Access Journals (Sweden)

    Margaret W. Ndinguri

    2012-01-01

    Full Text Available Cancer treatment by chemotherapy is typically accompanied by deleterious side effects, attributed to the toxic action of chemotherapeutics on proliferating cells from nontumor tissues. The cell surface proteoglycan CD44 has been recognized as a cancer stem cell marker. The present study has examined CD44 targeting as a way to selectively deliver therapeutic agents encapsulated inside colloidal delivery systems. CD44/chondroitin sulfate proteoglycan binds to a triple-helical sequence derived from type IV collagen, α1(IV1263–1277. We have assembled a peptide-amphiphile (PA in which α1(IV1263–1277 was sandwiched between 4 repeats of Gly-Pro-4-hydroxyproline and conjugated to palmitic acid. The PA was incorporated into liposomes composed of DSPG, DSPC, cholesterol, and DSPE-PEG-2000 (1 : 4 : 5 : 0.5. Doxorubicin-(DOX-loaded liposomes with and without 10% α1(IV1263–1277 PA were found to exhibit similar stability profiles. Incubation of DOX-loaded targeted liposomes with metastatic melanoma M14#5 and M15#11 cells and BJ fibroblasts resulted in IC50 values of 9.8, 9.3, and >100 μM, respectively. Nontargeted liposomes were considerably less efficacious for M14#5 cells. In the CD44+ B16F10 mouse melanoma model, CD44-targeted liposomes reduced the tumor size to 60% of that of the untreated control, whereas nontargeted liposomes were ineffective. These results suggest that PA targeted liposomes may represent a new class of nanotechnology-based drug delivery systems.

  10. Short antimicrobial peptides as cosmetic ingredients to deter dermatological pathogens.

    Science.gov (United States)

    Rahnamaeian, Mohammad; Vilcinskas, Andreas

    2015-11-01

    Antimicrobial peptides (AMPs) are components of the innate immune system in many species of animals. Their diverse spectrum of activity against microbial pathogens, both as innate defense molecules and immunomodulators, makes them attractive candidates for the development of a new generation of antibiotics. Although the potential immunogenicity of AMPs means they are not suitable for injection and their susceptibility to digestive peptidases is likely to reduce their oral efficacy, they are ideal for topical formulations such as lotions, creams, shampoos, and wound dressings and could therefore be valuable products for the cosmetic industry. In this context, short AMPs (care products. PMID:26307444

  11. Development of an effective gene delivery system: a study of complexes composed of a peptide-based amphiphilic DNA compaction agent and phospholipid

    Science.gov (United States)

    Murphy, Eric A.; Waring, Alan J.; Murphy, Jason C.; Willson, Richard C.; Longmuir, Kenneth J.

    2001-01-01

    We recently described a basic technology to efficiently combine compacted DNA with phospholipids and hydrophobic peptides, to produce homogenous complexes that are completely resistant to nuclease. We have developed this technology further to form gene delivery complexes that transfect cells effectively in vitro. In addition to plasmid DNA, the complexes contained two basic components: (i) a DNA compacting peptide (-CGKKKFKLKH), either conjugated to lipid or extended to contain (WLPLPWGW-) and (ii) either phosphatidylethanolamine or phosphatidylcholine. Complexes containing a 5.5-fold charge equivalence (peptide charge/DNA charge) of WLPLPWGWCGKKKFKLKH and 5 nmol dimyristoleoylphosphatidylethanolamine/µg DNA produced the highest luciferase gene expression, exceeding 1 × 109 relative light units/s/mg protein (>3 µg luciferase per mg protein). These complexes transfected OVCAR-3, COS-7 and HeLa cells at either similar or superior levels when compared to polyethylenimine or lipofectamine complexes. With green fluorescent protein reporter gene, >50% of HeLa cells were positive 30 h after addition of these complexes. Furthermore, these optimal complexes were the least sensitive to pre-treatment of cells with chloroquine, indicating efficient endosomal escape. Our results indicated that self-assembling complexes of plasmid DNA, amphiphilic peptide and phosphatidylethanolamine are highly effective non-viral gene delivery systems. PMID:11522841

  12. 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.

  13. Engineering Short Preorganized Peptide Sequences for Metal Ion Coordination: Copper(II) a Case Study.

    Science.gov (United States)

    Lima, L M P; Iranzo, O

    2016-01-01

    Peptides are multidentate chiral ligands capable of coordinating different metal ions. Nowadays, they can be obtained with high yield and purity, thanks to the advances on peptide/protein chemistry as well as in equipment (peptide synthesizers). Based on the identity and length of their amino acid sequences, peptides can present different degrees of flexibility and folding. Although short peptide sequences (ion coordination. Based on our experience, we present a general scheme for the design, synthesis, and characterization of these peptidic scaffolds and provide protocols for the study of their metal ion coordination properties.

  14. Multi-Composite Bioactive Osteogenic Sponges Featuring Mesenchymal Stem Cells, Platelet-Rich Plasma, Nanoporous Silicon Enclosures, and Peptide Amphiphiles for Rapid Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Dongmei Fan

    2011-06-01

    Full Text Available A novel bioactive sponge was created with a composite of type I collagen sponges or porous poly(e-caprolactone (PCL scaffolds, platelet-rich plasma (PRP, BMP2-loaded nanoporous silicon enclosure (NSE microparticles, mineralizing peptide amphiphiles (PA, and mesenchymal stem cells (MSC. Primary MSC from cortical bone (CB  tissue proved to form more and larger colony units, as well as produce more mineral matrix under osteogenic differentiation, than MSC from bone marrow (BM. Coating pre-treatments were optimized for maximum cell adhesion and mineralization, while a PRP-based gel carrier was created to efficiently deliver and retain MSC and  microparticles within a porous scaffold while simultaneously promoting cell recruitment, proliferation, and angiogenesis. Components and composite sponges were evaluated for osteogenic differentiation in vitro. Osteogenic sponges were loaded with MSC, PRP, PA, and NSE and implanted subcutaneously in rats to evaluate the formation of bone tissue and angiogenesis in vivo. It was found that the combination of a collagen sponge with CB MSC, PRP, PA, and the BMP2-releasing NSE formed the most bone and was most vascularized by four weeks compared to analogous composites featuring BM MSC or PCL or lacking PRP, PA, and NSE. This study indicates that CB MSC should be considered as an alternative to marrow as a source of stem cells, while the PRP-PA cell and microparticle delivery system may be utilized for diverse tissue engineering applications.

  15. 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.

  16. Role of peptide bond in the realization of biological activity of short peptides.

    Science.gov (United States)

    Khavinson, V Kh; Tarnovskaya, S I; Lin'kova, N S; Chervyakova, N A; Nichik, T E; Elashkina, E V; Chalisova, N I

    2015-02-01

    We performed a comparative analysis of biological activity of Lys-Glu peptide and its amino acid constituents. It was established that Lys-Glu stimulated proliferation of splenic cells in organotypic culture, while the mixture of glutamic acid and lysine inhibited culture growth. Using the method of molecular docking, we showed that glutamic acid, lysine, and Lys-Glu peptide can interact with different DNA sequences. The energy of interaction and the most beneficial localization of glutamic acid, lysine, and Lys-Glu peptide in DNA molecule was calculated. We demonstrated the interaction of the peptide and amino acids with DNA along the minor groove. The energy of DNA interaction with the peptide is higher than with individual amino acids. The peptide bonds increase the interaction of Lys-Glu peptide with DNA, which potentiates the biological effect on cell proliferation in organotypic culture of splenic cells.

  17. An effective conjugation strategy for designing short peptide-based HIV-1 fusion inhibitors.

    Science.gov (United States)

    Liang, Guodong; Wang, Huixin; Chong, Huihui; Cheng, Siqi; Jiang, Xifeng; He, Yuxian; Wang, Chao; Liu, Keliang

    2016-08-16

    Lengthy peptides corresponding to the C-terminal heptad repeat (C-peptides) of human immunodeficiency virus type 1 (HIV-1) gp41 are potent inhibitors against virus-cell fusion. Designing short C-peptide-based HIV-1 fusion inhibitors could potentially redress the physicochemical and technical liabilities of a long-peptide therapeutic. However, designing such inhibitors with high potency has been challenging. We generated a conjugated architecture by incorporating small-molecule inhibitors of gp41 into the N-terminus of a panel of truncated C-peptides. Among these small molecule-capped short peptides, the 26-residue peptide Indole-T26 inhibited HIV-1 Env-mediated cell-cell fusion and viral replication at low nanomolar levels, reaching the potency of the only clinically used 36-residue peptide T20 (enfuvirtide). Collectively, our work opens up a new avenue for developing short peptide-based HIV-1 fusion inhibitors, and may have broad applicability to the development of modulators of other class I fusion proteins. PMID:27454320

  18. The synthesis of new amphiphilic p-tert-butylthiacalix[4]arenes containing peptide fragments and their interaction with DNA.

    Science.gov (United States)

    Padnya, Pavel L; Andreyko, Elena A; Mostovaya, Olga A; Rizvanov, Ildar Kh; Stoikov, Ivan I

    2015-06-01

    New water-soluble p-tert-butylthiacalix[4]arenes containing peptide and quaternary ammonium fragments in cone and 1,3-alternate conformations were synthesized and characterized. The interaction of the macrocycles with DNA was studied by UV-spectroscopy, DLS and TEM. It was shown that the interaction of the self-associates based on p-tert-butylthiacalix[4]arenes tetrasubstituted at the lower rim with glycine and quaternary ammonium fragments in cone and 1,3-alternate conformations with DNA led to the formation of particles of about 99-192 nm in size.

  19. Novel short antibacterial and antifungal peptides with low cytotoxicity: Efficacy and action mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Qi, Xiaobao; Zhou, Chuncai; Li, Peng [School of Chemical and Biomedical Engineering, Nanyang Technological University, 62 Nanyang Drive, 637459 Singapore (Singapore); Xu, Weixin [School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, 637551 Singapore (Singapore); Cao, Ye; Ling, Hua; Ning Chen, Wei; Ming Li, Chang; Xu, Rong [School of Chemical and Biomedical Engineering, Nanyang Technological University, 62 Nanyang Drive, 637459 Singapore (Singapore); Lamrani, Mouad [Menicon Co., Ltd. Immeuble Espace Cordeliers, 2, rue President Carnot, 69002 Lyon (France); Mu, Yuguang, E-mail: ygmu@ntu.edu.sg [School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, 637551 Singapore (Singapore); Leong, Susanna Su Jan [School of Chemical and Biomedical Engineering, Nanyang Technological University, 62 Nanyang Drive, 637459 Singapore (Singapore); Wook Chang, Matthew, E-mail: matthewchang@ntu.edu.sg [School of Chemical and Biomedical Engineering, Nanyang Technological University, 62 Nanyang Drive, 637459 Singapore (Singapore); Chan-Park, Mary B., E-mail: mbechan@ntu.edu.sg [School of Chemical and Biomedical Engineering, Nanyang Technological University, 62 Nanyang Drive, 637459 Singapore (Singapore)

    2010-07-30

    Research highlights: {yields} Short antimicrobial peptides with nine and eleven residues were developed. {yields} These peptides show strong bactericidal activity against clinically important bacterial and fungal pathogens. {yields} These peptides exhibit high stability in the presence of salts, and low cytotoxicity. {yields} These peptides exert their action by disrupting membrane lipids. -- Abstract: Short antimicrobial peptides with nine and eleven residues were developed against several clinically important bacterial and fungal pathogens (specifically Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Candida albicans, and Fusarium solani). Twelve analogues of previously reported peptides BP76 (KKLFKKILKFL) and Pac-525 (KWRRWVRWI) were designed, synthesized, and tested for their antimicrobial activities. Two of our eleven amino acid peptides, P11-5 (GKLFKKILKIL) and P11-6 (KKLIKKILKIL), have very low MICs of 3.1-12.5 {mu}g ml{sup -1} against all five pathogens. The MICs of these two peptides against S. aureus, C. albicans and F. solani are four to ten times lower than the corresponding MICs of the reference peptide BP76. P9-4 (KWRRWIRWL), our newly designed nine-amino acid analogue, also has particularly low MICs of 3.1-6.2 {mu}g ml{sup -1} against four of the tested pathogens; these MICs are two to eight times lower than those reported for Pac-525 (6.2-50 {mu}g ml{sup -1}).These new peptides (P11-5, P11-6 and P9-4) also exhibit improved stability in the presence of salts, and have low cytotoxicity as shown by the hemolysis and MTT assays. From the results of field-emission scanning electron microscopy, membrane depolarization and dye-leakage assays, we propose that these peptides exert their action by disrupting membrane lipids. Molecular dynamics simulation studies confirm that P11-6 peptide maintains relatively stable helical structure and exerts more perturbation action on the order of acyl tail of lipid bilayer.

  20. Engineering Short Preorganized Peptide Sequences for Metal Ion Coordination: Copper(II) a Case Study.

    Science.gov (United States)

    Lima, L M P; Iranzo, O

    2016-01-01

    Peptides are multidentate chiral ligands capable of coordinating different metal ions. Nowadays, they can be obtained with high yield and purity, thanks to the advances on peptide/protein chemistry as well as in equipment (peptide synthesizers). Based on the identity and length of their amino acid sequences, peptides can present different degrees of flexibility and folding. Although short peptide sequences (structure in solution, different levels of structural preorganization can be induced by introducing conformational constraints, such as β-turn/loop template sequences and backbone cyclization. For all these reasons, and the fact that one is not restricted to use proteinogenic amino acids, small peptidic scaffolds constitute a simple and versatile platform for the development of inorganic systems with tailor-made properties and functions. Here we outline a general approach to the design of short preorganized peptide sequences (10-16 amino acids) for metal ion coordination. Based on our experience, we present a general scheme for the design, synthesis, and characterization of these peptidic scaffolds and provide protocols for the study of their metal ion coordination properties. PMID:27586340

  1. Interaction of short peptides with FITC-labeled wheat histones and their complexes with deoxyribooligonucleotides.

    Science.gov (United States)

    Fedoreyeva, L I; Smirnova, T A; Kolomijtseva, G Ya; Khavinson, V Kh; Vanyushin, B F

    2013-02-01

    Judging from fluorescence modulation (quenching), short peptides (Ala-Glu-Asp-Gly, Glu-Asp-Arg, Ala-Glu-Asp-Leu, Lys-Glu-Asp-Gly, Ala-Glu-Asp-Arg, and Lys-Glu-Asp-Trp) bind with FITC-labeled wheat histones H1, H2B, H3, and H4. This results from the interaction of the peptides with the N-terminal histone regions that contain respective and seemingly homologous peptide-binding motifs. Because homologous amino acid sequences in wheat core histones were not found, the peptides seem to bind with some core histone regions having specific conformational structure. Peptide binding with histones and histone-deoxyribooligonucleotide complexes depends on the nature of the histone and the primary structures of the peptides and oligonucleotides; thus, it is site specific. Histones H1 bind preferentially with single-stranded oligonucleotides by homologous sites in the C-terminal region of the protein. Unlike histone H1, the core histones bind predominantly with double-stranded methylated oligonucleotides and methylated DNA. Stern-Volmer constants of interaction of histone H1 and core histones with double-stranded hemimethylated oligonucleotides are higher compared with that of binding with unmethylated ones. DNA or deoxyribooligonucleotides in a complex with histones can enhance or inhibit peptide binding. It is suggested that site-specific interactions of short biologically active peptides with histone tails can serve in chromatin as control epigenetic mechanisms of regulation of gene activity and cellular differentiation.

  2. Short antimicrobial peptides as cosmetic ingredients to deter dermatological pathogens

    OpenAIRE

    Rahnamaeian, Mohammad; Vilcinskas, Andreas

    2015-01-01

    Antimicrobial peptides (AMPs) are components of the innate immune system in many species of animals. Their diverse spectrum of activity against microbial pathogens, both as innate defense molecules and immunomodulators, makes them attractive candidates for the development of a new generation of antibiotics. Although the potential immunogenicity of AMPs means they are not suitable for injection and their susceptibility to digestive peptidases is likely to reduce their oral efficacy, they are i...

  3. Design and characterization of short antimicrobial peptides using leucine zipper templates with selectivity towards microorganisms.

    Science.gov (United States)

    Ahmad, Aqeel; Azmi, Sarfuddin; Srivastava, Saurabh; Kumar, Amit; Tripathi, Jitendra Kumar; Mishra, Nripendra N; Shukla, Praveen K; Ghosh, Jimut Kanti

    2014-11-01

    Design of antimicrobial peptides with selective activity towards microorganisms is an important step towards the development of new antimicrobial agents. Leucine zipper sequence has been implicated in cytotoxic activity of naturally occurring antimicrobial peptides; moreover, this motif has been utilized for the design of novel antimicrobial peptides with modulated cytotoxicity. To understand further the impact of substitution of amino acids at 'a' and/or 'd' position of a leucine zipper sequence of an antimicrobial peptides on its antimicrobial and cytotoxic properties four short peptides (14-residue) were designed on the basis of a leucine zipper sequence without or with replacement of leucine residues in its 'a' and 'd' positions with D-leucine or alanine or proline residue. The original short leucine zipper peptide (SLZP) and its D-leucine substituted analog, DLSA showed comparable activity against the tested Gram-positive and negative bacteria and the fungal strains. The alanine substituted analog (ASA) though showed appreciable activity against the tested bacteria, it showed to some extent lower activity against the tested fungi. However, the proline substituted analog (PSA) showed lower activity against the tested bacterial or fungal strains. Interestingly, DLSA, ASA and PSA showed significantly lower cytotoxicity than SLZP against both human red blood cells (hRBCs) and murine 3T3 cells. Cytotoxic and bactericidal properties of these peptides matched with peptide-induced damage/permeabilization of mammalian cells and bacteria or their mimetic lipid vesicles suggesting cell membrane could be the target of these peptides. As evidenced by tryptophan fluorescence and acrylamide quenching studies the peptides showed similarities either in interaction or in their localization within the bacterial membrane mimetic negatively charged lipid vesicles. Only SLZP showed localization inside the mammalian membrane mimetic zwitterionic lipid vesicles. The results show

  4. Purification of a Novel Antibacterial Short Peptide in Earthworm Eisenia foetida

    Institute of Scientific and Technical Information of China (English)

    Yan-Qin LIU; Zhen-Jun SUN; Chong WANG; Shi-Jie LI; Yu-Zhi LIU

    2004-01-01

    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".

  5. 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.

  6. Blood-brain barrier transport of short proline-rich antimicrobial peptides.

    Science.gov (United States)

    Stalmans, Sofie; Wynendaele, Evelien; Bracke, Nathalie; Knappe, Daniel; Hoffmann, Ralf; Peremans, Kathelijne; Polis, Ingeborgh; Burvenich, Christian; De Spiegeleer, Bart

    2014-04-01

    Infections by antibiotic-resistant bacteria are becoming a great risk for human health, leading to an urgent need for new efficient antibacterial therapies. The short, proline-rich antimicrobial peptides from insects gained a lot of interest as a potential antibacterial treatment, having a low toxicity profile and being mainly active against Gram-negative bacteria. To know whether these antimicrobial peptides can be used for the treatment of cerebral infections, the blood-brain barrier transport characteristics of these peptides were investigated. This study describes the results of the in vivo blood-brain barrier experiments in mice, as well as the in vitro metabolic stability in mouse plasma and brain of apidaecin Api137, oncocin, drosocin and drosocin Pro5Hyp. The four investigated peptides showed a significant influx into the brain with a K(in) ranging between 0.37 and 0.86 µL/g x min and brain distribution volumes of 19.6 to 25.8 µL/g. Only for drosocin, a significant efflux was determined, with a k(out) of 0.22 min(-1). After entering the brain, oncocin was for approximately 80% trapped in the endothelial cells, while the other peptides reached the brain parenchyma for about 70%. All peptides were stable in plasma and brain during the experiments, with estimated metabolic half-lives ranging between 47 min and 637 min. We conclude that the investigated short, proline-rich antimicrobial peptides show an influx into the brain, which make them a promising antibacterial treatment of cerebral infections.

  7. Evaluation of short synthetic antimicrobial peptides for treatment of drug-resistant and intracellular Staphylococcus aureus.

    Science.gov (United States)

    Mohamed, Mohamed F; Abdelkhalek, Ahmed; Seleem, Mohamed N

    2016-01-01

    Methicillin-resistant Staphylococcus aureus (MRSA) infections present a serious challenge because of the emergence of resistance to numerous conventional antibiotics. Due to their unique mode of action, antimicrobial peptides are novel alternatives to traditional antibiotics for tackling the issue of bacterial multidrug resistance. Herein, we investigated the antibacterial activity of two short novel peptides (WR12, a 12 residue peptide composed exclusively of arginine and tryptophan, and D-IK8, an eight residue β-sheet peptide) against multidrug resistant staphylococci. In vitro, both peptides exhibited good antibacterial activity against MRSA, vancomycin-resistant S. aureus, linezolid-resistant S. aureus, and methicillin-resistant S. epidermidis. WR12 and D-IK8 were able to eradicate persisters, MRSA in stationary growth phase, and showed significant clearance of intracellular MRSA in comparison to both vancomycin and linezolid. In vivo, topical WR12 and D-IK8 significantly reduced both the bacterial load and the levels of the pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in MRSA-infected skin lesions. Moreover, both peptides disrupted established in vitro biofilms of S. aureus and S. epidermidis significantly more so than traditional antimicrobials tested. Taken together, these results support the potential of WR12 and D-IK8 to be used as a topical antimicrobial agent for the treatment of staphylococcal skin infections. PMID:27405275

  8. Control of the orientational order and nonlinear optical response of the "push-pull" chromophore RuPZn via specific incorporation into densely packed monolayer ensembles of an amphiphilic 4-helix bundle peptide: second harmonic generation at high chromophore densities.

    Science.gov (United States)

    Gonella, Grazia; Dai, Hai-Lung; Fry, H Christopher; Therien, Michael J; Krishnan, Venkata; Tronin, Andrey; Blasie, J Kent

    2010-07-21

    The macroscopic nonlinear optical response of the "push-pull" chromophore RuPZn incorporated into a single monolayer of the amphiphilic 4-helix bundle peptide (AP0) covalently attached to a solid substrate at high in-plane density has been measured. The second-order susceptibility, chi(zzz), was found to be in the range of approximately 15 x 10(-9) esu, consistent with a coherent sum of the nonlinear contributions from the individual chromophores (beta) as previously measured in isotropic solution through hyper-Rayleigh scattering as well as estimated from theoretical calculations. The microscopic hyperpolarizability of the RuPZn chromophore is preserved upon incorporation into the peptide monolayer, suggesting that the chromophore-chromophore interactions in the densely packed ensemble do not substantially affect the first-order molecular hyperpolarizability. The polarization angle dependence of the second harmonic signal reveals that the chromophore is vectorially oriented in the two-dimensional ensemble. Analysis of the order parameter together with information obtained from grazing incidence X-ray diffraction help in determining the chromophore orientation within the AP0-RuPZn monolayer. Taking into account an average pitch angle of approximately 20 degrees characterizing the coiled-coil structure of the peptide bundle, the width of the bundle's tilt angle distribution should be sigma < or = 20 degrees, resulting in a mean value of the tilt angle 23 degrees < or = theta(0) < or = 37 degrees. PMID:20578696

  9. Multilayered Short Peptide-Alginate Blends as New Materials for Potential Applications in Cartilage Tissue Regeneration.

    Science.gov (United States)

    Knoll, Grant A; Romanelli, Steven M; Brown, Alexandra M; Sortino, Rachel M; Banerjee, Ipsita A

    2016-03-01

    Peptide based nanomaterials have been gaining increased prominence due to their ability to form permeable scaffolds that promote growth and regeneration of new tissue. In this work for the first time a short hexapeptide motif VQIVYK, derived from the Tau protein family was conjugated with an organic polyamine linker, putrescine and utilized as a template for developing new materials for cartilage tissue regeneration. Our results showed that the conjugate formed extensive nanofibrous assemblies upon self-assembly under aqueous conditions. We then employed the layer-by-layer (LBL) approach to design the scaffold by first incorporating a short segment of the dentin sialophosphoprotein motif GDASYNSDESK followed by integration with the peptide sequence GSGAGAGSGAGAGSGAGA. This sequence mimics Ala, Gly, Ser repeats seen in the spider silk protein. We then incorporated the polysaccharide alginate which served as a hydrogel. To further enhance binding interactions with chondrocytes, and promote the formation of cartilage in vitro, the bionanocomposites were then attached to the chondrocyte binding peptide sequence HDSQLEALIKFM. The thermal properties as well as biodegradability of the scaffold was examined. To confirm biocompatibility, we examined cell viability, attachment and morphology in the presence of bovine chondrocytes. The cells were found to efficiently adhere to the scaffolds which formed an intricate mesh mimicking the extracellular matrix of cartilage tissue. To evaluate if differentiation occurred in the presence of the scaffolds, we examined in vitro deposition of proteoglycans. Thus, we have developed a new family of nanoscale scaffolds that may be utilized for cartilage tissue regeneration.

  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. PMID:12654759

  11. Computational Amphiphilic Materials for Drug Delivery

    Directory of Open Access Journals (Sweden)

    Naresh eThota

    2015-10-01

    Full Text Available Amphiphilic materials can assemble into a wide variety of morphologies and have emerged as a novel class of candidates for drug delivery. Along with a large number of experiments reported, computational studies have been also conducted in this field. At an atomistic/molecular level, computations can facilitate quantitative understanding of experimental observations and secure fundamental interpretation of underlying phenomena. This review summarizes the recent computational efforts on amphiphilic copolymers and peptides for drug delivery. Atom-resolution and time-resolved insights are provided from bottom-up to microscopically elucidate the mechanisms of drug loading/release, which are indispensable in the rational screening and design of new amphiphiles for high-efficacy drug delivery.

  12. Penetration of short fluorescence-labeled peptides into the nucleus in HeLa cells and in vitro specific interaction of the peptides with deoxyribooligonucleotides and DNA.

    Science.gov (United States)

    Fedoreyeva, L I; Kireev, I I; Khavinson, V Kh; Vanyushin, B F

    2011-11-01

    Marked fluorescence in cytoplasm, nucleus, and nucleolus was observed in HeLa cells after incubation with each of several fluorescein isothiocyanate-labeled peptides (epithalon, Ala-Glu-Asp-Gly; pinealon, Glu-Asp-Arg; testagen, Lys-Glu-Asp-Gly). This means that short biologically active peptides are able to penetrate into an animal cell and its nucleus and, in principle they may interact with various components of cytoplasm and nucleus including DNA and RNA. It was established that various initial (intact) peptides differently affect the fluorescence of the 5,6-carboxyfluorescein-labeled deoxyribooligonucleotides and DNA-ethidium bromide complexes. The Stern-Volmer constants characterizing the degree of fluorescence quenching of various single- and double-stranded fluorescence-labeled deoxyribooligonucleotides with short peptides used were different depending on the peptide primary structures. This indicates the specific interaction between short biologically active peptides and nucleic acid structures. On binding to them, the peptides discriminate between different nucleotide sequences and recognize even their cytosine methylation status. Judging from corresponding constants of the fluorescence quenching, the epithalon, pinealon, and bronchogen (Ala-Glu-Asp-Leu) bind preferentially with deoxyribooligonucleotides containing CNG sequence (CNG sites are targets for cytosine DNA methylation in eukaryotes). Epithalon, testagen, and pinealon seem to preferentially bind with CAG- but bronchogen with CTG-containing sequences. The site-specific interactions of peptides with DNA can control epigenetically the cell genetic functions, and they seem to play an important role in regulation of gene activity even at the earliest stages of life origin and in evolution.

  13. The role of amphiphiles

    NARCIS (Netherlands)

    Hoekstra, F.A.; Golovina, E.A.

    2002-01-01

    This paper reviews our work on the partitioning of amphiphilic compounds from the cytoplasm into membranes during drying of plant systems, and discusses how relevant this phenomenon might be for anhydrobiosis. Amphiphilic guest molecules do partition into membranes and oil bodies, as demonstrated by

  14. Short-term aerobic exercise training improves gut peptide regulation in nonalcoholic fatty liver disease.

    Science.gov (United States)

    Kullman, Emily L; Kelly, Karen R; Haus, Jacob M; Fealy, Ciaran E; Scelsi, Amanda R; Pagadala, Mangesh R; Flask, Chris A; McCullough, Arthur J; Kirwan, John P

    2016-05-15

    Obesity-related nonalcoholic fatty liver disease (NAFLD) is now the most common chronic liver disease. Exercise and diet are uniformly prescribed treatments for NAFLD; however, there are limited empirical data on the effects of exercise training on metabolic function in these patients. The purpose of this study was to investigate the fasting and glucose-stimulated adaptation of gut peptides to short-term aerobic exercise training in patients with NAFLD. Twenty-two obese subjects, 16 with NAFLD [body mass index (BMI), 33.2 ± 1.1 (SE) kg/m(2)] and 6 obese controls (BMI, 31.3 ± 1.2 kg/m(2)), were enrolled in a supervised aerobic exercise program (60 min/day, 85% of their heart rate maximum, for 7 days). Fasting and glucose-stimulated glucagon-like peptide-1 (GLP-17-36) and peptide tyrosine tyrosine (PYYTotal) concentrations in plasma were assessed before and after the exercise program. Initially, the NAFLD group had higher fasting PYY (NAFLD = 117 ± 18.6, control = 47.2 ± 6.4 pg/ml, P obese adults with NAFLD. PMID:27032902

  15. Endocytosis and Trafficking of Natriuretic Peptide Receptor-A: Potential Role of Short Sequence Motifs

    Directory of Open Access Journals (Sweden)

    Kailash N. Pandey

    2015-07-01

    Full Text Available The targeted endocytosis and redistribution of transmembrane receptors among membrane-bound subcellular organelles are vital for their correct signaling and physiological functions. Membrane receptors committed for internalization and trafficking pathways are sorted into coated vesicles. Cardiac hormones, atrial and brain natriuretic peptides (ANP and BNP bind to guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA and elicit the generation of intracellular second messenger cyclic guanosine 3',5'-monophosphate (cGMP, which lowers blood pressure and incidence of heart failure. After ligand binding, the receptor is rapidly internalized, sequestrated, and redistributed into intracellular locations. Thus, NPRA is considered a dynamic cellular macromolecule that traverses different subcellular locations through its lifetime. The utilization of pharmacologic and molecular perturbants has helped in delineating the pathways of endocytosis, trafficking, down-regulation, and degradation of membrane receptors in intact cells. This review describes the investigation of the mechanisms of internalization, trafficking, and redistribution of NPRA compared with other cell surface receptors from the plasma membrane into the cell interior. The roles of different short-signal peptide sequence motifs in the internalization and trafficking of other membrane receptors have been briefly reviewed and their potential significance in the internalization and trafficking of NPRA is discussed.

  16. Mixed α/β-Peptides as a Class of Short Amphipathic Peptide Hydrogelators with Enhanced Proteolytic Stability.

    Science.gov (United States)

    Mangelschots, Jeroen; Bibian, Mathieu; Gardiner, James; Waddington, Lynne; Van Wanseele, Yannick; Van Eeckhaut, Ann; Acevedo, Maria M Diaz; Van Mele, Bruno; Madder, Annemieke; Hoogenboom, Richard; Ballet, Steven

    2016-02-01

    Peptide hydrogels are a highly promising class of materials for biomedical application, albeit facing many challenges with regard to stability and tunability. Here, we report a new class of amphipathic peptide hydrogelators, namely mixed α/β-peptide hydrogelators. These mixed α/β-gelators possess good rheological properties (high storage moduli) and form transparent self-supporting gels with shear-thinning behavior. Infrared spectroscopy indicates the presence of β-sheets as the underlying secondary structure. Interestingly, self-assembled nanofibers of the mixed α/β-peptides display unique structural morphologies with alteration of the C-terminus (acid vs amide) playing a key role in the fiber formation and gelation properties of the resulting hydrogels. The incorporation of β3-homoamino acid residues within the mixed α/β-peptide gelators led to an increase in proteolytic stability of the peptides under nongelating conditions (in solution) as well as gelating conditions (as hydrogel). Under diluted conditions, degradation of mixed α/β-peptides in the presence of elastase was slowed down 120-fold compared to that of an α-peptide, thereby demonstrating beneficial enzymatic resistance for hydrogel applications in vivo. In addition, increased half-life values were obtained for the mixed α/β-peptides in human blood plasma, as compared to corresponding α-peptides. It was also found that the mixed α/β-peptides were amenable to injection via needles used for subcutaneous administrations. The preformed peptide gels could be sheared upon injection and were found to quickly reform to a state close to that of the original hydrogel. The shown properties of enhanced proteolytic stability and injectability hold great promise for the use of these novel mixed α/β-peptide hydrogels for applications in the areas of tissue engineering and drug delivery. PMID:26741458

  17. 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.

  18. Self-assembly of small peptide amphiphiles, the structures formed and their applications. (A foods and home and personal care perspective).

    Science.gov (United States)

    Frith, W J

    2016-07-28

    In this opinion piece, some specific challenges in the field of peptide self-assembly and gel formation are discussed. One major hurdle to finding functional small peptides is that there are a huge number of compounds to explore, which increases exponentially with the peptide size. This in itself creates a barrier to the discovery and application of materials, both through the difficulty of finding the peptides, and because protecting inventions also becomes more difficult. Recent work has shown that computer simulations may provide us a route to explore such a huge compound space; this is discussed along with the prospect for future developments. At the microscopic scale, many fibril-forming peptides form gels, apparently through a process of lateral association of primary self-assembled filaments, which leads to a relatively coarse-grained structure of rigid interconnects. However, recent data obtained on Fmoc-tyrosine gels appear to indicate that the gel microstructure is both more flexible and finer grained than previously believed. As such, it is clear that there is a considerable amount that is still not understood regarding this class of gel.This article is part of the themed issue 'Soft interfacial materials: from fundamentals to formulation'. PMID:27298432

  19. 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 ...

  20. End-tagging of ultra-short antimicrobial peptides by W/F stretches to facilitate bacterial killing.

    Directory of Open Access Journals (Sweden)

    Mukesh Pasupuleti

    Full Text Available BACKGROUND: Due to increasing resistance development among bacteria, antimicrobial peptides (AMPs, are receiving increased attention. Ideally, AMP should display high bactericidal potency, but low toxicity against (human eukaryotic cells. Additionally, short and proteolytically stable AMPs are desired to maximize bioavailability and therapeutic versatility. METHODOLOGY AND PRINCIPAL FINDINGS: A facile approach is demonstrated for reaching high potency of ultra-short antimicrobal peptides through end-tagging with W and F stretches. Focusing on a peptide derived from kininogen, KNKGKKNGKH (KNK10 and truncations thereof, end-tagging resulted in enhanced bactericidal effect against Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus. Through end-tagging, potency and salt resistance could be maintained down to 4-7 amino acids in the hydrophilic template peptide. Although tagging resulted in increased eukaryotic cell permeabilization at low ionic strength, the latter was insignificant at physiological ionic strength and in the presence of serum. Quantitatively, the most potent peptides investigated displayed bactericidal effects comparable to, or in excess of, that of the benchmark antimicrobial peptide LL-37. The higher bactericidal potency of the tagged peptides correlated to a higher degree of binding to bacteria, and resulting bacterial wall rupture. Analogously, tagging enhanced peptide-induced rupture of liposomes, particularly anionic ones. Additionally, end-tagging facilitated binding to bacterial lipopolysaccharide, both effects probably contributing to the selectivity displayed by these peptides between bacteria and eukaryotic cells. Importantly, W-tagging resulted in peptides with maintained stability against proteolytic degradation by human leukocyte elastase, as well as staphylococcal aureolysin and V8 proteinase. The biological relevance of these findings was demonstrated ex vivo for pig skin infected by S. aureus and

  1. Design and evaluation of antimalarial peptides derived from prediction of short linear motifs in proteins related to erythrocyte invasion.

    Directory of Open Access Journals (Sweden)

    Alessandra Bianchin

    Full Text Available The purpose of this study was to investigate the blood stage of the malaria causing parasite, Plasmodium falciparum, to predict potential protein interactions between the parasite merozoite and the host erythrocyte and design peptides that could interrupt these predicted interactions. We screened the P. falciparum and human proteomes for computationally predicted short linear motifs (SLiMs in cytoplasmic portions of transmembrane proteins that could play roles in the invasion of the erythrocyte by the merozoite, an essential step in malarial pathogenesis. We tested thirteen peptides predicted to contain SLiMs, twelve of them palmitoylated to enhance membrane targeting, and found three that blocked parasite growth in culture by inhibiting the initiation of new infections in erythrocytes. Scrambled peptides for two of the most promising peptides suggested that their activity may be reflective of amino acid properties, in particular, positive charge. However, one peptide showed effects which were stronger than those of scrambled peptides. This was derived from human red blood cell glycophorin-B. We concluded that proteome-wide computational screening of the intracellular regions of both host and pathogen adhesion proteins provides potential lead peptides for the development of anti-malarial compounds.

  2. 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

    2016-06-01

    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 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.

  3. Whey peptide-based enteral diet attenuated elastase-induced emphysema with increase in short chain fatty acids in mice

    OpenAIRE

    Tomoda, Koichi; Kubo, Kaoru; Dairiki, Kazuo; Yamaji, Taketo; Yamamoto, Yoshifumi; Nishii, Yasue; Nakamura, Atsuhiro; Yoshikawa, Masanori; Hamada, Kaoru; Kimura, Hiroshi

    2015-01-01

    Background Systemic inflammation is present in chronic obstructive pulmonary disease (COPD). A whey peptide-based enteral diet reduce inflammation in patients with COPD, but its effect on COPD development has not been determined. On the other hand, it is known that short chain fatty acids (SCFAs), which are produced by micro-flora in the gut, attenuates bronchial asthma in mice model. Methods Mice with elastase-induced emphysema were fed with 1 of 3 diets (control diet, whey peptide-based ent...

  4. Self-assembly of short peptides to form hydrogels: design of building blocks, physical properties and technological applications.

    Science.gov (United States)

    Fichman, Galit; Gazit, Ehud

    2014-04-01

    Hydrogels are unique supramolecular solid-like assemblies composed mainly of water molecules that are held by molecular networks. Physical hydrogels that are formed by a set of non-covalent interactions to establish a well-ordered scaffold devoid of any chemical cross-linking are especially intriguing for various biotechnological and medical applications. Peptides are particularly interesting building blocks of physical gels because of the role of polypeptides as structural elements in biological systems, the extensive ability for their chemical and biological decoration and functionalization, and the facile synthesis of natural and modified peptides. This review describes the assembly and properties of physical hydrogels that have been formed by the self-association of very simple peptide building blocks. Natural short peptides, as short as dipeptides, can form ordered gel assemblies. Moreover, in the case of N-terminal protection, even a protected amino acid can serve as an efficient hydrogelator. Further elucidation of hydrogelators' assembly, as well as the characterization of their physical properties, can guide the rational design of building blocks for a desired application. The possible mechanism of self-assembly is discussed in line with the chemical nature of the short peptides. Different methods have been used to induce hydrogel assembly, which may significantly affect the mechanical characteristics of the resulting gels. Here, special emphasis is given to methods that allow either spatial control of hydrogel formation or modulation of physical properties of the gel. Finally, the parameters that influence hydrogelation are described, and insights for their design are provided. PMID:23958781

  5. Molecular Bases for the Recognition of Short Peptide Substrates and Cysteine-Directed Modifications of Human Insulin-Degrading Enzyme

    Energy Technology Data Exchange (ETDEWEB)

    Malito, Enrico; Ralat, Luis A.; Manolopoulou, Marika; Tsay, Julie L.; Wadlington, Natasha L.; Tang, Wei-Jen (UC)

    2009-12-01

    Insulin degrading enzyme (IDE) utilizes a large catalytic chamber to selectively bind and degrade peptide substrates such as insulin and amyloid {beta} (A{beta}). Tight interactions with substrates occur at an exosite located 30 {angstrom} away from the catalytic center that anchors the N-terminus of substrates to facilitate binding and subsequent cleavages at the catalytic site. However, IDE also degrades peptide substrates that are too short to occupy both the catalytic site and the exosite simultaneously. Here, we use kinins as a model system to address the kinetics and regulation of human IDE with short peptides. IDE specifically degrades bradykinin and kallidin at the Pro/Phe site. A 1.9 {angstrom} crystal structure of bradykinin-bound IDE reveals the binding of bradykinin to the exosite and not to the catalytic site. In agreement with observed high K{sub m} values, this suggests low affinity of bradykinin for IDE. This structure also provides the molecular basis on how the binding of short peptides at the exosite could regulate substrate recognition. We also found that human IDE is potently inhibited by physiologically relevant concentrations of S-nitrosylation and oxidation agents. Cysteine-directed modifications play a key role, since an IDE mutant devoid of all 13 cysteines is insensitive to the inhibition by S-nitrosoglutathione, hydrogen peroxide, or N-ethylmaleimide. Specifically, cysteine 819 of human IDE is located inside the catalytic chamber pointing toward an extended hydrophobic pocket and is critical for the inactivation. Thiol-directed modification of this residue likely causes local structural perturbation to reduce substrate binding and catalysis.

  6. Molecular bases for the recognition of short peptide substrates and cysteine-directed modifications of human insulin-degrading enzyme

    Science.gov (United States)

    Malito, Enrico; Ralat, Luis A.; Manolopoulou, Marika; Tsay, Julie L.; Wadlington, Natasha L.; Tang, Wei-Jen

    2009-01-01

    Insulin degrading enzyme (IDE) utilizes a large catalytic chamber to selectively bind and degrade peptide substrates such as insulin and amyloid β (Aβ). Tight interactions with substrates occur at an exosite located ~30Å away from the catalytic center that anchors the N-terminus of substrates to facilitate binding and subsequent cleavages at the catalytic site. However, IDE also degrades peptide substrates that are too short to occupy both the catalytic site and the exosite simultaneously. Here, we use kinins as a model system to address the kinetics and regulation of human IDE with short peptides. IDE specifically degrades bradykinin and kallidin at the Pro/Phe site. A 1.9Å crystal structure of bradykinin-bound IDE reveals the binding of bradykinin to the exosite, and not to the catalytic site. In agreement with observed high Km values, this suggests low affinity of bradykinin for IDE. This structure also provides the molecular basis on how the binding of short peptides at the exosite could regulate substrate recognition. We also found that human IDE is potently inhibited by physiologically relevant concentrations of S-nitrosylation and oxidation agents. Cysteine-directed modifications play a key role, since an IDE mutant devoid of all thirteen cysteines is insensitive to the inhibition by S-nitroso-glutathione, hydrogen peroxide, or N-ethylmaleimide. Specifically, cysteine 819 of human IDE is located inside the catalytic chamber pointing towards an extended hydrophobic pocket and is critical for the inactivation. Thiol-directed modification of this residue likely causes local structural perturbation to reduce substrate binding and catalysis. PMID:18986166

  7. Self-assembly of amphiphilic molecules:A review on the recent computer simulation results

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    We provided a short review on the recent progresses in computer simulations of adsorption and self-assembly of amphiphilic molecules.Owing to the extensive applications of amphiphilic molecules,it is very important to understand thoroughly the effects of the detailed chemistry,solid surfaces and the degree of confinement on the aggregate morphologies and kinetics of self-assembly for amphiphilic systems.In this review we paid special attention on(i) morphologies of adsorbed surfactants on solid surfaces,(ii) self-assembly in confined systems,and(iii) kinetic processes involving amphiphilic molecules.

  8. Antimicrobial activity, improved cell selectivity and mode of action of short PMAP-36-derived peptides against bacteria and Candida.

    Science.gov (United States)

    Lyu, Yinfeng; Yang, Yang; Lyu, Xiting; Dong, Na; Shan, Anshan

    2016-01-01

    Antimicrobial peptides (AMPs) have recently attracted a great deal of attention as promising antibiotic candidates, but some obstacles such as toxicity and high synthesis cost must be addressed before developing them further. For developing short peptides with improved cell selectivity, we designed a series of modified PMAP-36 analogues. Antimicrobial assays showed that decreasing chain length in a certain range retained the high antimicrobial activity of the parental peptide and reduced hemolysis. The 18-mer peptide RI18 exhibited excellent antimicrobial activity against both bacteria and fungi, and its hemolytic activity was observably lower than PMAP-36 and melittin. The selectivity indexes of RI18 against bacteria and fungi were improved approximately 19-fold and 108-fold, respectively, compared to PMAP-36. In addition, serum did not affect the antibacterial activity of RI18 against E. coli but inhibited the antifungal efficiency against C. albicans. Flow cytometry and electron microscopy observation revealed that RI18 killed microbial cells primarily by damaging membrane integrity, leading to whole cell lysis. Taken together, these results suggest that RI18 has potential for further therapeutic research against frequently-encountered bacteria and fungi. Meanwhile, modification of AMPs is a promising strategy for developing novel antimicrobials to overcome drug-resistance. PMID:27251456

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

    Directory of Open Access Journals (Sweden)

    Lock J

    2011-11-01

    Full Text Available Jaclyn Lock, Huinan Liu Department of Bioengineering, University of California, Riverside, CA, USA 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. Keywords: human mesenchymal stem cells, osteogenesis, stem cell differentiation, bone morphogenetic protein, peptide delivery, nanocomposites

  10. Competitive Binding of Natural Amphiphiles with Graphene Derivatives

    Science.gov (United States)

    Radic, Slaven; Geitner, Nicholas K.; Podila, Ramakrishna; Käkinen, Aleksandr; Chen, Pengyu; Ke, Pu Chun; Ding, Feng

    2013-07-01

    Understanding the transformation of graphene derivatives by natural amphiphiles is essential for elucidating the biological and environmental implications of this emerging class of engineered nanomaterials. Using rapid discrete-molecular-dynamics simulations, we examined the binding of graphene and graphene oxide with peptides, fatty acids, and cellulose, and complemented our simulations by experimental studies of Raman spectroscopy, FTIR, and UV-Vis spectrophotometry. Specifically, we established a connection between the differential binding and the conformational flexibility, molecular geometry, and hydrocarbon content of the amphiphiles. Importantly, our dynamics simulations revealed a Vroman-like competitive binding of the amphiphiles for the graphene oxide substrate. This study provides a mechanistic basis for addressing the transformation, evolution, transport, biocompatibility, and toxicity of graphene derivatives in living systems and the natural environment.

  11. Aggregation properties of a short peptide that mediates amyloid fibril formation in model proteins unrelated to disease

    Indian Academy of Sciences (India)

    Nitin Chaudhary; Shashi Singh; Ramakrishnan Nagaraj

    2011-09-01

    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 chicken brain -spectrin, which is otherwise non-amyloidogenic, is rendered amyloidogenic if 22EVTMKK27 is replaced by DIDLHL. In this article, we describe the aggregation behaviour of DIDLHL-COOH and DIDLHL-CONH2. Our results indicate that DIDLHL-COOH and DIDLHL-CONH2 aggregate to form spherical structures at pH 5 and 6. At pH 5, in the presence of mica, DIDLHL-CONH2 forms short fibrous structures. The presence of NaCl along with mica results in fibrillar structures. At pH 6, DIDLHL-CONH2 forms largely spherical aggregates. Both the peptides are unstructured in solution but adopt -conformation on drying. The aggregates formed by DIDLHL-COOH and DIDLHL-CONH2 are formed during drying process and their structures are modulated by the presence of mica and salt. Our study suggests that a peptide need not have intrinsic amyloidogenic propensity to facilitate the selfassembly of the full-length protein. The propensity of peptides to form self-assembled structures that are non-amyloidogenic could be important in potentiating the self-assembly of full-length proteins into amyloid fibrils.

  12. 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.

  13. Linear short histidine and cysteine modified arginine peptides constitute a potential class of DNA delivery agents.

    Science.gov (United States)

    Mann, Anita; Shukla, Vasundhara; Khanduri, Richa; Dabral, Spoorti; Singh, Harpal; Ganguli, Munia

    2014-03-01

    The success of gene therapy relies on the development of safe and efficient multifunctional carriers of nucleic acids that can overcome extra- and intracellular barriers, protect the nucleic acid and mediate its release at the desired site allowing gene expression. Peptides bear unique properties that are indispensable for any carrier, e.g., they can mediate DNA condensation, cellular targeting, membrane translocation, endosomal escape and nuclear localization. In an effort to design a multifunctional peptide, we have modified an arginine homopeptide R16 by replacement of seven arginines with histidines and addition of one cysteine at each end respectively to impart endosomal escape property while maintaining the DNA condensation and release balance. Addition of histidines imparts endosomal escape property to arginine homopeptide, but their arrangement with respect to arginines is more critical in controlling DNA condensation, release and transfection efficiency. Intriguingly, R5H7R4 peptide where charge/arginine is distributed in blocks is preferred for strong condensation while more efficient transfection is seen in the variants R9H7 and H4R9H3, which exhibit weak condensation and strong release. Addition of cysteine to each of these peptides further fine-tuned the condensation-release balance without application of any oxidative procedure unlike other similar systems reported in the literature. This resulted in a large increase in the transfection efficiency in all of the histidine modified peptides irrespective of the arginine and histidine positions. This series of multifunctional peptides shows comparable transfection efficiency to commercially available transfection reagent Lipofectamine 2000 at low charge ratios, with simple preparative procedure and exhibits much less toxicity. PMID:24476132

  14. Sticky tubes and magnetic hydrogels co-assembled by a short peptide and melanin-like nanoparticles.

    Science.gov (United States)

    Das, Priyadip; Yuran, Sivan; Yan, Jian; Lee, Pooi See; Reches, Meital

    2015-03-28

    This communication describes the co-assembly of polydopamine spheres, either bare or coated with Fe3O4 magnetic nanoparticles, with the short aromatic peptide diphenylalanine. The combination of polydopamine particles and diphenylalanine generated tubular structures decorated with adhesive spherical particles, while the co-assembly of the polydopamine spheres coated with magnetic Fe3O4 nanoparticles with diphenylalanine resulted in the formation of a magnetic hydrogel. These new architectures may be useful as new vehicles for several applications including tissue regeneration and drug delivery. PMID:25470201

  15. 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....

  16. Short Peptide Nucleic Acids Bind Strongly to Homopurine Tract of Double Helical RNA at pH 5.5

    OpenAIRE

    Li, Ming; Zengeya, Thomas; Rozners, Eriks

    2010-01-01

    The important role that non-coding RNA plays in cell biology makes it an attractive target for molecular recognition. However, the discovery of small molecules that bind double helical RNA selectively and may serve as biochemical probes and potential drug leads has been relatively slow. Herein, we show that peptide nucleic acids, as short as six nucleobases, bind very strongly (Ka > 107) and sequence selectively to a homopurine tract of double helical RNA at pH 5.5. The isothermal titration c...

  17. A proline-derived transannular N-cap for nucleation of short α-helical peptides.

    Science.gov (United States)

    Tian, Yuan; Wang, Dongyuan; Li, Jingxu; Shi, Chuan; Zhao, Hui; Niu, Xiaogang; Li, Zigang

    2016-07-28

    We report herein a proline-derived transannular N-cap as a helix nucleating template in diverse bio-related peptide sequences via macrolactamization on resin. This approach takes advantage of synergistic stabilization effects of both N-capping properties of proline and substitution of a main chain hydrogen bond with a covalent bond. PMID:27357119

  18. 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

  19. 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...... and even micellar inversion. On contrary, the bulky geometry of the tryptophan residue in KAnW limits the variation of the surfactant parameter and hence largely prevents assembly into spherical or cylindrical micelles while favouring flatter geometries. The studied short peptide families demonstrate...

  20. Acute effects of the Glucagon-Like Peptide 2 analogue, teduglutide, on intestinal adaptation in newborn pigs with short bowel syndrome

    DEFF Research Database (Denmark)

    Thymann, Thomas; Stoll, Barbara; Mecklenburg, Lars;

    2014-01-01

    Neonatal short bowel syndrome following massive gut resection associates with malabsorption of nutrients. The intestinotrophic factor glucagon-like peptide 2 (GLP-2) improves gut function in adult short bowel patients, but its effect in pediatric patients remains unknown. Our objective was to tes...

  1. Amphiphilic dendronized homopolymers

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    A series of second generation of amphiphilic dendronized homopolymers are efficiently synthesized,and their thermoresponsiveness in aqueous solutions and secondary structures in methanol solutions are described.These polymers are constructed in each repeat unit with various generations of hydrophobic 4-aminoproline and hydrophilic oligoethylene glycol (OEG)-based dendrons,and their over-all hydrophilicity is tuned by varying these dendron generations.Polymers with or without the first generation of proline dendron show good water solubility at room temperature,but exhibit typical thermoresponsive behaviors at elevated temperatures as characterized by turbidity measurements using UV-vis spectroscopy,while the polymer with the secondary generation of proline dendron is not soluble in water.All polymers show ordered secondary structures as evidenced by the optical rotation and circular dichroism experiments.Finally,assembly of these amphiphilic homopolymers into porous films via breath figure (BF) technique is described,and polymer structures are found to show significant influence on the morphology of porous film.

  2. 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

  3. Aqueous Foam Stabilized by Tricationic Amphiphilic Surfactants

    Science.gov (United States)

    Heerschap, Seth; Marafino, John; McKenna, Kristin; Caran, Kevin; Feitosa, Klebert; Kevin Caran's Research Group Collaboration

    2015-03-01

    The unique surface properties of amphiphilic molecules have made them widely used in applications where foaming, emulsifying or coating processes are needed. The development of novel architectures with multi-cephalic/tailed molecules have enhanced their anti-bacterial activity in connection with tail length and the nature of the head group. Here we report on the foamability of two triple head double, tail cationic surfactants (M-1,14,14, M-P, 14,14) and a triple head single tail cationic surfactant (M-1,1,14) and compare them with commercially available single headed, single tailed anionic and cationic surfactants (SDS,CTAB and DTAB). The results show that bubble rupture rate decrease with the length of the carbon chain irrespective of head structure. The growth rate of bubbles with short tailed surfactants (SDS) and longer, single tailed tricationic surfactants (M-1,1,14) was shown to be twice as high as those with longer tailed surfactants (CTAB, M-P,14,14, M-1,14,14). This fact was related to the size variation of bubbles, where the foams made with short tail surfactants exhibited higher polydispersivity than those with short tails. This suggests that foams with tricationic amphiphilics are closed linked to their tail length and generally insensitive to their head structure.

  4. Efficient Cargo Delivery into Adult Brain Tissue Using Short Cell-Penetrating Peptides.

    Directory of Open Access Journals (Sweden)

    Caghan Kizil

    Full Text Available Zebrafish brains can regenerate lost neurons upon neurogenic activity of the radial glial progenitor cells (RGCs that reside at the ventricular region. Understanding the molecular events underlying this ability is of great interest for translational studies of regenerative medicine. Therefore, functional analyses of gene function in RGCs and neurons are essential. Using cerebroventricular microinjection (CVMI, RGCs can be targeted efficiently but the penetration capacity of the injected molecules reduces dramatically in deeper parts of the brain tissue, such as the parenchymal regions that contain the neurons. In this report, we tested the penetration efficiency of five known cell-penetrating peptides (CPPs and identified two- polyR and Trans - that efficiently penetrate the brain tissue without overt toxicity in a dose-dependent manner as determined by TUNEL staining and L-Plastin immunohistochemistry. We also found that polyR peptide can help carry plasmid DNA several cell diameters into the brain tissue after a series of coupling reactions using DBCO-PEG4-maleimide-based Michael's addition and azide-mediated copper-free click reaction. Combined with the advantages of CVMI, such as rapidness, reproducibility, and ability to be used in adult animals, CPPs improve the applicability of the CVMI technique to deeper parts of the central nervous system tissues.

  5. Influence of Amphibian Antimicrobial Peptides and Short Lipopeptides on Bacterial Biofilms Formed on Contact Lenses

    Directory of Open Access Journals (Sweden)

    Magdalena Maciejewska

    2016-10-01

    Full Text Available The widespread use of contact lenses is associated with several complications, including ocular biofilm-related infections. They are very difficult to manage with standard antimicrobial therapies, because bacterial growth in a biofilm is associated with an increased antibiotic resistance. The principal aim of this study was to evaluate the efficacy of antimicrobial peptides (AMPs in eradication of bacterial biofilms formed on commercially available contact lenses. AMPs were synthesized according to Fmoc/tBu chemistry using the solid-phase method. Minimum inhibitory concentration (MIC and minimum biofilm eradication concentration (MBEC of the compounds were determined. Anti-biofilm activity of the antimicrobial peptides determined at different temperatures (25 °C and 37 °C were compared with the effectiveness of commercially available contact lens solutions. All of the tested compounds exhibited stronger anti-biofilm properties as compared to those of the tested lens solutions. The strongest activity of AMPs was noticed against Gram-positive strains at a temperature of 25 °C. Conclusions: The results of our experiments encourage us toward further studies on AMPs and their potential application in the prophylaxis of contact lens-related eye infections.

  6. Nasal Levels of Antimicrobial Peptides in Allergic Asthma Patients and Healthy Controls: Differences and Effect of a Short 1,25(OH2 Vitamin D3 Treatment.

    Directory of Open Access Journals (Sweden)

    Willemien Thijs

    Full Text Available Allergy is often accompanied by infections and lower levels of antimicrobial peptides (AMPs. Vitamin D has been shown to increase expression of selected AMPs. In this study we investigated whether antimicrobial peptide levels in nasal secretions of allergic asthma patients are lower than in healthy controls, and whether administration of the active form of vitamin D (1,25(OH2D3 affects these antimicrobial peptide levels.The levels of antimicrobial peptides in nasal secretions were compared between 19 allergic asthma patients and 23 healthy controls. The effect of seven days daily oral treatment with 2 μg 1,25(OH2D3 on antimicrobial peptides in nasal secretions was assessed in a placebo-controlled cross-over clinical study.Levels of neutrophil α-defensins (human neutrophil peptides 1-3; HNP1-3 and lipocalin 2 (LCN2; also known as NGAL were significantly lower in asthmatics, but no differences in LL-37 and SLPI were detected. Treatment with a short-term 1,25(OH2D3 caused a small increase in HNP1-3, but not when the asthma and control groups were analyzed separately. LL-37, LCN2 and SLPI did not change after treatment with 1,25(OH2D3.Levels of the antimicrobial peptides HNP1-3 and LCN2 are lower in nasal secretions in asthmatics and are not substantially affected by a short-term treatment with active vitamin D.

  7. Effect of amino acid substitution in the hydrophobic face of amphiphilic peptides on membrane curvature and perturbation: N-terminal helix derived from adenovirus internal protein VI as a model.

    Science.gov (United States)

    Murayama, Tomo; Pujals, Sílvia; Hirose, Hisaaki; Nakase, Ikuhiko; Futaki, Shiroh

    2016-11-01

    The N-terminal amphipathic helical segment of adenovirus internal protein VI (AdVpVI) plays a critical role in viral infection. Here, we report that the peptide segment corresponding to AdVpVI (positions 33-55) can induce positive membrane curvature together with membrane perturbation. The enhanced perturbation ability of the peptide was observed for membranes containing negatively charged phospholipids. Based on the liposome leakage assay, substitution of leucine at position 40 to other aliphatic (isoleucine) and aromatic (phenylalanine and tryptophan) residues yielded a similar degree of membrane perturbation by the peptides, which was considerably diminished by the substitution to glutamine. Further studies using the wild-type AdVpVI (33-55) (WT) and phenylalanine-substituted peptides (L40F) demonstrated that both peptides have positive membrane-curvature-inducing ability. These peptides showed higher binding affinity to 50-nm large unilamellar vesicles (LUVs) than to 200-nm LUVs. However, no enhanced perturbation by these peptides was observed for 50-nm LUVs compared to 200-nm LUVs, suggesting that both the original membrane curvature and the additional strain due to peptide insertion affect the membrane perturbation ability of these peptides. In the case of L40F, this peptide rather had a lower membrane perturbation ability for 50-nm LUVs than for 200-nm LUVs, which can be attributed to possible shallower binding of L40F on membranes. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 430-439, 2016. PMID:27271816

  8. Short-days induce weight loss in Siberian hamsters despite overexpression of the agouti-related peptide gene.

    Science.gov (United States)

    Jethwa, P H; Warner, A; Fowler, M J; Murphy, M; de Backer, M W; Adan, R A H; Barrett, P; Brameld, J M; Ebling, F J P

    2010-06-01

    Many vertebrates express profound annual cycles of body fattening, although it is not clear whether these represent differential activity of the central pathways known to mediate homeostatic control of food intake and energy expenditure, or whether the recent discovery of a major role for pars tuberalis-ependymal signalling points towards novel mechanisms. We examined this in the Siberian hamster (Phodopus sungorus) by using gene transfection to up-regulate a major orexigenic peptide, agouti-related peptide (AgRP), and then determined whether this increased anabolic drive could prevent the short-day induced winter catabolic state. Infusions of a recombinant adeno-associated virus encoding an AgRP construct into the hypothalamus of hamsters in the long-day obese phase of their seasonal cycle produced a 20% gain in body weight over 6 weeks compared to hamsters receiving a control reporter construct, reflecting a significant increase in food intake and a significant decrease in energy expenditure. However, all hamsters showed a significant, prolonged decrease in body weight when exposed to short photoperiods, despite the hamsters expressing the AgRP construct maintaining a higher food intake and lower energy expenditure relative to the control hamsters. Visualisation of the green fluorescent protein reporter and analysis of AgRP-immunoreactivity confirmed widespread expression of the construct in the hypothalamus, which was maintained for the 21-week duration of the study. In conclusion, the over-expression of AgRP in the hypothalamus produced a profoundly obese state but did not block the seasonal catabolic response, suggesting a separation of rheostatic mechanisms in seasonality from those maintaining homeostasis of energy metabolism.

  9. Conformational preference of 'CαNN' short peptide motif towards recognition of anions.

    Directory of Open Access Journals (Sweden)

    Tridip Sheet

    Full Text Available Among several 'anion binding motifs', the recently described 'C(αNN' motif occurring in the loop regions preceding a helix, is conserved through evolution both in sequence and its conformation. To establish the significance of the conserved sequence and their intrinsic affinity for anions, a series of peptides containing the naturally occurring 'C(αNN' motif at the N-terminus of a designed helix, have been modeled and studied in a context free system using computational techniques. Appearance of a single interacting site with negative binding free-energy for both the sulfate and phosphate ions, as evidenced in docking experiments, establishes that the 'C(αNN' segment has an intrinsic affinity for anions. Molecular Dynamics (MD simulation studies reveal that interaction with anion triggers a conformational switch from non-helical to helical state at the 'C(αNN' segment, which extends the length of the anchoring-helix by one turn at the N-terminus. Computational experiments substantiate the significance of sequence/structural context and justify the conserved nature of the 'C(αNN' sequence for anion recognition through "local" interaction.

  10. Morphogenic Peptides in Regeneration of Load Bearing Tissues.

    Science.gov (United States)

    Moeinzadeh, Seyedsina; Jabbari, Esmaiel

    2015-01-01

    Morphogenic proteins due to their short half-life require high doses of growth factors in regeneration of load bearing tissues which leads to undesirable side effects. These side effects include bone overgrowth, tumor formation and immune reaction. An alternative approach to reduce undesirable side effects of proteins in regenerative medicine is to use morphogenic peptides derived from the active domains of morphogenic proteins or soluble and insoluble components of the extracellular matrix of mineralized load bearing tissues to induce differentiation of progenitor cells, mineralization, maturation and bone formation. In that regard, many peptides with osteogenic activity have been discovered. These include peptides derived from bone morphogenic proteins (BMPs), those based on interaction with integrin and heparin-binding receptors, collagen derived peptides, peptides derived from other soluble ECM proteins such as bone sialoprotein and enamel matrix proteins, and those peptides derived from vasculoinductive and neuro-inductive proteins. Although these peptides show significant osteogenic activity in vitro and increase mineralization and bone formation in animal models, they are not widely used in clinical orthopedic applications as an alternative to morphogenic proteins. This is partly due to the limited availability of data on structure and function of morphogenic peptides in physiological medium, particularly in tissue engineered scaffolds. Due to their amphiphilic nature, peptides spontaneously self-assemble and aggregate into micellar structures in physiological medium. Aggregation alters the sequence of amino acids in morphogenic peptides that interact with cell surface receptors thus affecting osteogenic activity of the peptide. Aggregation and micelle formation can dramatically reduce the active concentration of morphogenic peptides with many-fold increase in peptide concentration in physiological medium. Other factors that affect bioactivity are the non

  11. 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

  12. Evolutionarily conserved and conformationally constrained short peptides might serve as DNA recognition elements in intrinsically disordered regions.

    Science.gov (United States)

    Tayal, Nitish; Choudhary, Preeti; Pandit, Shashi B; Sandhu, Kuljeet Singh

    2014-06-01

    Despite recent advances, it is yet not clear how intrinsically disordered regions in proteins recognize their targets without any defined structures. Short linear motifs had been proposed to mediate molecular recognition by disordered regions; however, the underlying structural prerequisite remains elusive. Moreover, the role of short linear motifs in DNA recognition has not been studied. We report a repertoire of short evolutionarily Conserved Recognition Elements (CoREs) in long intrinsically disordered regions, which have very distinct amino-acid propensities from those of known motifs, and exhibit a strong tendency to retain their three-dimensional conformations compared to adjacent regions. The majority of CoREs directly interact with the DNA in the available 3D structures, which is further supported by literature evidence, analyses of ΔΔG values of DNA-binding energies and threading-based prediction of DNA binding potential. CoREs were enriched in cancer-associated missense mutations, further strengthening their functional nature. Significant enrichment of glycines in CoREs and the preference of glycyl ϕ-Ψ values within the left-handed bridge range in the l-disallowed region of the Ramachandran plot suggest that Gly-to-nonGly mutations within CoREs might alter the backbone conformation and consequently the function, a hypothesis that we reconciled using available mutation data. We conclude that CoREs might serve as bait for DNA recognition by long disordered regions and that certain mutations in these peptides can disrupt their DNA binding potential and consequently the protein function. We further hypothesize that the preferred conformations of CoREs and of glycyl residues therein might play an important role in DNA binding. The highly ordered nature of CoREs hints at a therapeutic strategy to inhibit malicious molecular interactions using small molecules mimicking CoRE conformations.

  13. Amphiphiles for protein solubilization and stabilization

    Science.gov (United States)

    Gellman, Samuel Helmer; Chae, Pil Seok; Laible, Philip D.; Wander, Marc J.

    2012-09-11

    The invention provides amphiphiles for manipulating membrane proteins. The amphiphiles can feature carbohydrate-derived hydrophilic groups and branchpoints in the hydrophilic moiety and/or in a lipophilic moiety. Such amphiphiles are useful as detergents for solubilization and stabilization of membrane proteins, including photosynthetic protein superassemblies obtained from bacterial membranes.

  14. Structural and optical properties of short peptides: nanotubes-to-nanofibers phase transformation.

    Science.gov (United States)

    Handelman, Amir; Natan, Amir; Rosenman, Gil

    2014-07-01

    Thermally induced phase transformation in bioorganic nanotubes, which self-assembled from two ultrashort dipeptides of different origin, aromatic diphenylalanine (FF) and aliphatic dileucine (LL), is studied. In both FF and LL nanotubes, irreversible phase transformation found at 120-180 °C is governed by linear-to-cyclic dipeptide molecular modification followed by formation of extended β-sheet structure. As a result of this process, native open-end FF and LL nanotubes are transformed into ultrathin nanofibrils. Found deep reconstructions at all levels from macroscopic (morphology) and structural space symmetry to molecular give rise to new optical properties in both aromatic FF and aliphatic LL nanofibrils and generation of blue photoluminescence (PL) emission. It is shown that observed blue PL peak is similar in these supramolecular nanofibrillar structures and is excited by the network of non-covalent hydrogen bonds that link newly thermally induced neighboring cyclic dipeptide strands to final extended β-sheet structure of amyloid-like nanofibrils. The observed blue PL peak in short dipeptide nanofibrils is similar to the blue PL peak that was recently found in amyloid fibrils and can be considered as the optical signature of β-sheet structures. Nanotubular structures were characterized by environmental scanning electron microscope, ToF-secondary ion mass spectroscopy, CD and fluorescence spectroscopy. PMID:24895323

  15. High-affinity binding of short peptides to major histocompatibility complex class II molecules by anchor combinations.

    OpenAIRE

    Hammer, J.; Belunis, C; Bolin, D; Papadopoulos, J.; Walsky, R; Higelin, J; Danho, W; Sinigaglia, F; Nagy, Z A

    1994-01-01

    We have previously identified four anchor positions in HLA-DRB1*0101-binding peptides, and three anchors involved in peptide binding to DRB1*0401 and DRB1*1101 molecules, by screening of an M13 peptide display library (approximately 20 million independent nonapeptides) for DR-binding activity. In this study, high stringency screening of the M13 library for DRB1*0401 binding has resulted in identification of three further anchor positions. Taken together, a peptide-binding motif has been obtai...

  16. Nanostructured Amphiphilic Star-Hyperbranched Block Copolymers for Drug Delivery.

    Science.gov (United States)

    Seleci, Muharrem; Seleci, Didem Ag; Ciftci, Mustafa; Demirkol, Dilek Odaci; Stahl, Frank; Timur, Suna; Scheper, Thomas; Yagci, Yusuf

    2015-04-21

    A robust drug delivery system based on nanosized amphiphilic star-hyperbranched block copolymer, namely, poly(methyl methacrylate-block-poly(hydroxylethyl methacrylate) (PMMA-b-PHEMA) is described. PMMA-b-PHEMA was prepared by sequential visible light induced self-condensing vinyl polymerization (SCVP) and conventional vinyl polymerization. All of the synthesis and characterization details of the conjugates are reported. To accomplish tumor cell targeting property, initially cell-targeting (arginylglycylaspactic acid; RGD) and penetrating peptides (Cys-TAT) were binding to each other via the well-known EDC/NHS chemistry. Then, the resulting peptide was further incorporated to the surface of the amphiphilic hyperbranched copolymer via a coupling reaction between the thiol (-SH) group of the peptide and the hydroxyl group of copolymer by using N-(p-maleinimidophenyl) isocyanate as a heterolinker. The drug release property and targeting effect of the anticancer drug (doxorobucin; DOX) loaded nanostructures to two different cell lines were evaluated in vitro. U87 and MCF-7 were chosen as integrin αvβ3 receptor positive and negative cells for the comparison of the targeting efficiency, respectively. The data showed that drug-loaded copolymers exhibited enhanced cell inhibition toward U87 cells in compared to MCF-7 cells because targeting increased the cytotoxicity of drug-loaded copolymers against integrin αvβ3 receptor expressing tumor cells. PMID:25816726

  17. Vibrational analysis of amino acids and short peptides in aqueous media. V. The effect of the disulfide bridge on the structural features of the peptide hormone somatostatin-14.

    Science.gov (United States)

    Hernández, Belén; Carelli, Claude; Coïc, Yves-Marie; De Coninck, Joël; Ghomi, Mahmoud

    2009-09-24

    To emphasize the role played by the S-S bridge in the structural features of somatostatin-14 (SST-14), newly recorded CD and Raman spectra of this cyclic peptide and its open analogue obtained by Cys-->Ser substitution are presented. CD spectra of both peptides recorded in aqueous solutions in the 100-500 microM concentration range are strikingly similar. They reveal principally that random conformers constitute the major population in both peptides. Consequently, the S-S bridge has no structuring effect at submillimolar concentrations. In methanol, the CD spectrum of somatostatin-14 keeps globally the same spectral shape as that observed in water, whereas its open analogue presents a major population of helical conformers. Raman spectra recorded as a function of peptide concentration (5-20 mM) and also in the presence of 150 mM NaCl provide valuable conformational information. All Raman spectra present a mixture of random and beta-hairpin structures for both cyclic and open peptides. More importantly, the presence or the absence of the disulfide bridge does not seem to influence considerably different populations of secondary structures within this range of concentrations. CD and Raman data obtained in the submillimolar and millimolar ranges of concentrations, respectively, lead us to accept the idea that SST-14 monomers aggregate upon increasing concentration, thus stabilizing beta-hairpin conformations in solution. However, even at high concentrations, random conformers do not disappear. Raman spectra of SST-14 also reveal a concentration effect on the flexibility of the S-S linkage and consequently on that of its cyclic part. In conclusion, although the disulfide linkage does not seem to markedly influence the SST-14 conformational features in aqueous solutions, its presence seems to be necessary to ensure the flexibility of the cyclic part of this peptide and to maintain its closed structure in lower dielectric constant environments.

  18. Thermoresponsive giant biohybrid amphiphiles

    NARCIS (Netherlands)

    Lavigueur, Christine; Gonzalez Garcia, Jordi; Hendriks, Linda; Hoogenboom, Richard; Cornelissen, Jeroen J.L.M.; Nolte, Roeland J.M.

    2011-01-01

    A series of random copolymers of various lengths was prepared by atom transfer radical polymerisation (ATRP) using two acrylate monomers with short pendant ethylene glycol side chains (ethylene glycol methyl ether acrylate, EGMEA, and methoxy ethoxy ethyl acrylate, MEEA). The end group was converted

  19. A thermodynamic signature of lipid segregation in biomembranes induced by a short peptide derived from glycoprotein gp36 of feline immunodeficiency virus.

    Science.gov (United States)

    Oliva, Rosario; Del Vecchio, Pompea; Stellato, Marco Ignazio; D'Ursi, Anna Maria; D'Errico, Gerardino; Paduano, Luigi; Petraccone, Luigi

    2015-02-01

    The interactions between proteins/peptides and lipid bilayers are fundamental in a variety of key biological processes, and among these, the membrane fusion process operated by viral glycoproteins is one of the most important, being a fundamental step of the infectious event. In the case of the feline immunodeficiency virus (FIV), a small region of the membrane proximal external region (MPER) of the glycoprotein gp36 has been demonstrated to be necessary for the infection to occur, being able to destabilize the membranes to be fused. In this study, we report a physicochemical characterization of the interaction process between an eight-residue peptide, named C8, modeled on that gp36 region and some biological membrane models (liposomes) by using calorimetric and spectroscopic measurements. CD studies have shown that the peptide conformation changes upon binding to the liposomes. Interestingly, the peptide folds from a disordered structure (in the absence of liposomes) to a more ordered structure with a low but significant helix content. Isothermal titration calorimetry (ITC) and differential scanning calorimetry (DSC) results show that C8 binds with high affinity the lipid bilayers and induces a significant perturbation/reorganization of the lipid membrane structure. The type and the extent of such membrane reorganization depend on the membrane composition. These findings provide interesting insights into the role of this short peptide fragment in the mechanism of virus-cell fusion, demonstrating its ability to induce lipid segregation in biomembranes.

  20. 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. PMID:22431418

  1. The effect of Glucagon-Like Peptide-2 on mesenteric blood flow and cardiac parameters in end-jejunostomy short bowel patients

    DEFF Research Database (Denmark)

    Bremholm, Lasse; Hornum, Mads; Andersen, Ulrik B;

    2011-01-01

    Exogenous Glucagon-Like Peptide-2 (GLP-2) treatment improves intestinal wet weight absorption in short bowel syndrome (SBS) patients. In healthy subjects, administration of GLP-2 increases small intestinal blood flow. The aim of the study was to evaluate the effect of GLP-2 on mesenteric blood flow...... and dynamic changes in cardiac parameters in SBS patients with jejunostomy and varying length of remnant small intestine....

  2. Short-Chain Fatty Acids Stimulate Glucagon-Like Peptide-1 Secretion via the G-Protein-Coupled Receptor FFAR2

    OpenAIRE

    Tolhurst, Gwen; Heffron, Helen; Lam, Yu Shan; Parker, Helen E; Habib, Abdella M; Diakogiannaki, Eleftheria; Cameron, Jennifer; Grosse, Johannes; Reimann, Frank; Gribble, Fiona M.

    2012-01-01

    Interest in how the gut microbiome can influence the metabolic state of the host has recently heightened. One postulated link is bacterial fermentation of “indigestible” prebiotics to short-chain fatty acids (SCFAs), which in turn modulate the release of gut hormones controlling insulin release and appetite. We show here that SCFAs trigger secretion of the incretin hormone glucagon-like peptide (GLP)-1 from mixed colonic cultures in vitro. Quantitative PCR revealed enriched expression of the ...

  3. Short reaction of C-peptide, glucagon-like peptide-1, ghrelin and endomorphin-1 for different style diet in type 2 diabetic patients

    Institute of Scientific and Technical Information of China (English)

    CHEN Yi; WANG Xin; ZHANG Mei-fang; LI Yan-xiang; LI Ying; GU Ting; XIA Fang-zhen; YU Jiao; LU Ying-li

    2011-01-01

    Background Food composition and style is changing dramatically now,which causes inappropriate secretion of hormones from brain,gastrointestinal and endo-pancreas,may be related to unbalance of glucose in blood.The aim of this study was to explore the fast response of C-peptide,glucagon-like peptide-1 (GLP-1),ghrelin and endomorphin-1 (EM-1) to the eastern and western style meals in patients with type 2 diabetes mellitus.Methods The study enrolled 57 patients with type 2 diabetes (20 men and 37 women,mean age (67.05±8.26) years).Eastern style meal (meal A) and western style meal (meal B) were designed to produce the fullness effect.C-peptide,GLP-1,ghrelin and EM-1 were assessed before (0 hour) and after (2 hours) each diet.Results The delta (2h-0h) of C- peptide in meal A was significantly lower than that in meal B (P=0.0004).C-peptide,GLP-1,ghrelin and EM-1 were obviously higher before meal B than those before meal A (P <0.0001,<0.0001,=0.001,=0.0004 respectively).Blood glucose 2 hours and 3 hours after meal B were higher than those after meal A (P=-0.0005,0.0079 respectively).Correlations between GLP-1 and ghrelin were strongly positive before both meals and 2 hours after both meals and also in relation to the delta of meal A and meal B (rA0h=0.7836,rB0h=0.9368,rAsh=0.7615,rB2h=0.9409,rA(2h_0h)=0.7531,rB(2h-0h)=0.9980,respectively,P <0.0001).Conclusion Western style meal (high fat and protein food) could make more response of C-peptide than eastern style meal,and could stimulate more gut hormones (GLP-1,ghrelin) and brain peptide (EM-1) at the first phase of digestion.

  4. Peptide nanofibers modified with a protein by using designed anchor molecules bearing hydrophobic and functional moieties.

    Science.gov (United States)

    Miyachi, Ayaka; Takahashi, Tsuyoshi; Matsumura, Sachiko; Mihara, Hisakazu

    2010-06-11

    Self-assembly of peptides and proteins is a key feature of biological functions. Short amphiphilic peptides designed with a beta-sheet structure can form sophisticated nanofiber structures, and the fibers are available as nanomaterials for arranging biomolecules. Peptide FI (H-PKFKIIEFEP-OH) self-assembles into nanofibers with a coiled fine structure, as reported in our previous work. We have constructed anchor molecules that have both a binding moiety for the fiber structure and a functional unit capable of capturing target molecules, with the purpose of arranging proteins on the designed peptide nanofibers. Designed anchors containing an alkyl chain as a binding unit and biotin as a functional moiety were found to bind to peptide fibers FI and F2i (H-ALEAKFAAFEAKLA-NH(2)). The surface-exposed biotin moiety on the fibers could capture an anti-biotin antibody. Moreover, hydrophobic dipeptide anchor units composed of iminodiacetate connected to Phe-Phe or Ile-Ile and a peptide composed of six histidine residues connected to biotin could also connect FI peptide fibers to the anti-biotin antibody through the chelation of Ni(2+) ions. This strategy of using designed anchors opens a novel approach to constructing nanoscale protein arrays on peptide nanomaterials. PMID:20419712

  5. 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

  6. A novel short anionic antibacterial peptide isolated from the skin of Xenopus laevis with broad antibacterial activity and inhibitory activity against breast cancer cell.

    Science.gov (United States)

    Li, Siming; Hao, Linlin; Bao, Wanguo; Zhang, Ping; Su, Dan; Cheng, Yunyun; Nie, Linyan; Wang, Gang; Hou, Feng; Yang, Yang

    2016-07-01

    A vastarray of bioactive peptides from amphibian skin secretions is attracting increasing attention due to the growing problem of bacteria resistant to conventional antibiotics. In this report, a small molecular antibacterial peptide, named Xenopus laevis antibacterial peptide-P1 (XLAsp-P1), was isolated from the skin of Xenopus laevis using reversed-phase high-performance liquid chromatography. The primary structure of XLAsp-P1, which has been proved to be a novel peptide by BLAST search in AMP database, was DEDDD with a molecular weight of 607.7 Da analysed by Edman degradation and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/TOF-MS). The highlight of XLAsp-P1 is the strong in vitro potency against a variety of Gram-positive and Gram-negative bacteria with minimum inhibitory concentrations (MICs) starting at 10 μg/mL and potent inhibitory activity against breast cancer cell at tested concentrations from 5 to 50 μg/mL. In addition, only 6.2 % of red blood cells was haemolytic when incubated with 64 μg/mL (higher than MICs of all bacterial strain) of XLAsp-P1. The antimicrobial mechanism for this novel peptide was the destruction of the cell membrane investigated by transmission electron microscopy. All these showed that XLAsp-P1 is a novel short anionic antibacterial peptide with broad antibacterial activity and inhibitory activity against breast cancer cell. PMID:26952034

  7. Interfacial Templating of Inorganic Nanostructures Using Rationally Designed Peptide Molecules

    Science.gov (United States)

    Leon Gibbons, Lorraine

    In nature, biological molecules form interfaces that assemble patterns of chemical functionality with exceptional precision. The role of dynamics during the assembly of biological molecules appears to be important for mineralization processes. The work presented in this dissertation applies model sheet-forming peptides at interfaces to explore the dynamics of assembly in order to template mineral growth. The peptide molecules are rationally designed to have amphiphilic properties and a propensity for sheet-like secondary structure. These designed peptides are deposited at the air/water interface to explore the dynamics of their self-assembly and investigate their 2D order. To characterize the phase behavior, techniques such as Langmuir Blodgett and Brewster Angle Microscopy are used. In addition, we verify the hypothesized sheet-forming propensity using both Circular Dichroism and Attenuated Total Reflection Fourier Transform Infrared Spectroscopy, while the characterization of the inorganic phase is done using Transmission Electron Microscopy, Electron Diffraction, and Atomic Force Microscopy. Thermodynamic analysis of structure formation with increasing pressure allows us to understand the nature of self-assembly with iterative changes in the peptide sequence. Additionally, we look at the dynamics of the self-assembled state, where the organic phase switches between short- and long-range order as a function of surface pressure. We use this model system to explore the influence of electrostatic interactions on self-assembly, and additionally, the influence of short- and long-range order on the nucleation and growth of inorganic material. This is in contrast to a system that starts with a well-ordered preformed template that defines the epitaxial growth of the mineral phase. Two versions of our model peptides are constructed by substituting histidine for glutamic acid in order to nucleate Au nanocrystals in both the short and long range ordered organic matrix, to

  8. Tandem Facial Amphiphiles for Membrane Protein Stabilization

    DEFF Research Database (Denmark)

    Chae, Pil Seok; Gotfryd, Kamil; Pacyna, Jennifer;

    2010-01-01

    We describe a new type of synthetic amphiphile that is intended to support biochemical characterization of intrinsic membrane proteins. Members of this new family displayed favorable behavior with four of five membrane proteins tested, and these amphiphiles formed relatively small micelles....

  9. A Short Peptide That Mimics the Binding Domain of TGF-β1 Presents Potent Anti-Inflammatory Activity.

    Directory of Open Access Journals (Sweden)

    Emília R Vaz

    Full Text Available The transforming growth factor beta 1 (TGF-β1 is a pleiotropic cytokine with multiple roles in development, wound healing, and immune regulation. TGF-β1-mediated immune dysfunction may lead to pathological conditions, such as inflammation. Chronic inflammatory process is characterized by a continuous release of pro-inflammatory cytokines, and the inhibition or the blockage of these cytokines signaling pathways are considered a target treatment. In this context, despite the high numbers of TGF-β-targeted pathways, the inducible regulatory T cells (iTreg to control inflammation seems to be a promising approach. Our aim was to develop novel peptides through phage display (PhD technology that could mimic TGF-β1 function with higher potency. Specific mimetic peptides were obtained through a PhD subtraction strategy from whole cell binding using TGF-β1 recombinant as a competitor during elution step. We have selected a peptide that seems to play an important role on cellular differentiation and modulation of TNF-α and IL-10 cytokines. The synthetic pm26TGF-β1 peptide tested in PBMC significantly down-modulated TNF-α and up-regulated IL-10 responses, leading to regulatory T cells (Treg phenotype differentiation. Furthermore, the synthetic peptide was able to decrease leukocytes rolling in BALB/C mice and neutrophils migration during inflammatory process in C57BL/6 mice. These data suggest that this peptide may be useful for the treatment of inflammatory diseases, especially because it displays potent anti-inflammatory properties and do not exhibit neutrophils' chemoattraction.

  10. Single-chain crosslinked star polymers via intramolecular crosslinking of self-folding amphiphilic copolymers in water

    OpenAIRE

    Terashima, Takaya; Sugita, Takanori; Sawamoto, Mitsuo

    2015-01-01

    Single-chain crosslinked star polymers with multiple hydrophilic short arms and a hydrophobic core were created as novel microgel star polymers of single polymer chains. The synthetic process involves the intramolecular crosslinking of self-folding amphiphilic random copolymers in water. For this process, amphiphilic random copolymers bearing hydrophilic poly(ethylene glycol) (PEG) and hydrophobic olefin pendants were synthesized by ruthenium-catalyzed living radical copolymerization of PEG m...

  11. 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...

  12. HSPVdb—the Human Short Peptide Variation Database for improved mass spectrometry-based detection of polymorphic HLA-ligands

    NARCIS (Netherlands)

    Nijveen, H.; Kester, M.G.D.; Hassan, C.; Viars, A.; Ru, A.H.; Jager, de M.; Falkenburg, J.H.F.; Leunissen, J.A.M.; Veelen, van P.A.

    2011-01-01

    T cell epitopes derived from polymorphic proteins or from proteins encoded by alternative reading frames (ARFs) play an important role in (tumor) immunology. Identification of these peptides is successfully performed with mass spectrometry. In a mass spectrometry-based approach, the recorded tandem

  13. Elevated plasma glucagon-like peptide 1 and 2 concentrations in ileum resected short bowel patients with a preserved colon

    DEFF Research Database (Denmark)

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

    2000-01-01

    The glucagon-like peptides (GLP) 1 and 2 are secreted postprandially from L cells located mainly in the ileum. Both hormones prolong intestinal transit and GLP-2 is intestinotrophic in rodents. Patients with a jejunostomy have poor adaptation, rapid gastric and intestinal transit, and impaired po...

  14. Role of solution conformation and flexibility of short peptide ligands that bind to the p56(lck) SH2 domain

    NARCIS (Netherlands)

    Dekker, Frank J; de Mol, Nico J; Bultinck, Patrick; Kemmink, Johan; Hilbers, Hans W; Liskamp, Rob M J; Dekker, Frank

    2003-01-01

    A general approach in drug design is making ligands more rigid in order to avoid loss in conformational entropy (deltaS(conf)) upon receptor binding. We hypothesized that in the high affinity binding of pYEEI peptide ligands to the p56(lck) SH2 domain this loss in deltaS(conf) might be diminished du

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

    OpenAIRE

    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 fai...

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

    OpenAIRE

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

    2014-01-01

    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, an...

  17. Induction of Porcine Host Defense Peptide Gene Expression by Short-Chain Fatty Acids and Their Analogs

    OpenAIRE

    Zeng, Xiangfang; Sunkara, Lakshmi T; Jiang, Weiyu; Bible, Megan; Carter, Scott; Ma, Xi; Qiao, Shiyan; Zhang, Guolong

    2013-01-01

    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...

  18. 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, I.B.; Jeppesen, Palle Bekker; Hartmann, B.;

    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 (...... and therefore precludes treatment of their osteopenia with GLP-2. The anti-resorptive response to GLP-2 seems to require an intact small intestine and may involve suppression of PTH secretion Udgivelsesdato: 2008......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...

  19. 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 (...... and therefore precludes treatment of their osteopenia with GLP-2. The anti-resorptive response to GLP-2 seems to require an intact small intestine and may involve suppression of PTH secretion.......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...

  20. Amphiphilic Soft Janus Particles as Interfacial Stabilizers

    Science.gov (United States)

    Wang, Wenda; Niu, Sunny; Sosa, Chris; Prud'Homme, Robert; Priestley, Rodney; Priestley Polymer group Team; Prud'homme Research Group Team

    Janus particles, which incorporate two or more ``faces'' with different chemical functionality, have attracted great attention in scientific research. Amphiphilic Janus particles have two faces with distinctly different hydrophobicity. This can be thought of as colloidal surfactants. Theoretical studies on the stabilization of emulsions using Janus particles have confirmed higher efficiency. Herein we synthesize the narrow distributed amphiphilic polymeric Janus particles via Precipitation-Induced Self-Assembly (PISA). The efficiency of the amphiphilic Janus particles are tested on different oil/water systems. Biocompatible polymers can also be used on this strategy and may potentially have wide application for food emulsion, cosmetics and personal products.

  1. Preparation and Properties of Vesicles from Condensable Amphiphilic Amino Acids

    Institute of Scientific and Technical Information of China (English)

    熊向源; 何巍; 李子臣; 李福绵

    2001-01-01

    Three double-chain amphiphiles with amino acid groups as hydrphilic moiety were synthesized. These amphiphiles can be easily dispersed in buffer solution to form transparent dispersion. Examination of the dispersion by transmission electron microscopy (TEM) showed the formation of stable vesicular aggregates, which was also confirmed by the ability to encapsulate water-soluble dyes. Since amino acid groups are located on the surface of the vesicles, water-soluble carbodiimide can induce the condensation of these groups to form peptide. The phase transition temperatures of these vesicles were estimated by differential scanning calorimetry (DSC), and a decrease of phase transition temperature was observed after polycondensation due to the disturbance of the ordered arrangement of the hydrophobic chains. The leakage rate of the vesicles before and after condensation was studied by monitoring the increase of fluorescence intensity of water-soluble dye. These vesicles belong to the least permeable ones and the leakage rate can be controlled by varying the degree of condensation or the temperature.

  2. Structural characterization of the model amphipathic peptide Ac-LKKLLKLLKKLLKL-NH2 in aqueous solution and with 2,2,2-trifluoroethanol and 1,1,1,3,3,3-hexafluoroisopropanol

    Energy Technology Data Exchange (ETDEWEB)

    Buchko, Garry W.; Jain, Avijita; Reback, Matthew L.; Shaw, Wendy J.

    2013-06-03

    Short-chain amphiphilic peptides are promising components in the new generation of engineered biomaterials with many potential applications. The 14-residue leucine-lysine peptide Ac-LKKLLKLLKKLLKL-NH2 (LKα) is one such amphiphilic peptide. The periodic distribution of hydrophobic and hydrophilic amino acid residues in the sequence of LKα has been shown to promote α-helix formation in an ionic environment and at high peptide concentrations (> ~0.5 mM, no salt). Here, circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopy is used to demonstrate that LKα, in the absence of salt and at concentrations < 0.5 mM, readily adopts a helical structure in the presence of the structure stabilizing agents 2,2,2-trifluoroethanol (TFE) and 1,1,1,3,3,3-hexafluoroisopropanol (HFIP). Maximal helical character, as monitored by negative bands with double minima at 222 and 208-210 nm in the CD spectrum, was observed in 20% TFE and 10% HFIP (volume percent). The helical character suggested by the CD data was corroborated with amide to alpha proton, long range, 1HN(i) to 1Hα(i-3) NOEs characteristic of an α-helical structure. In unbuffered water in the absence of a flouronated alcohol and at low peptide concentrations, LKα was essentially unstructured in solution. These observations confirm that LKα has a predisposition to adopt a helical structure that may be maximized with minimal amounts of fluorinated alcohol. This characterization of the structural and physical properties of LKα will assist the design of future biomaterials containing amphiphilic peptides.

  3. [Study of novel artificial lung surfactants incorporating partially fluorinated amphiphiles].

    Science.gov (United States)

    Nakahara, Hiromichi

    2012-01-01

    Lung surfactants (LS), a complex of ∼90 wt% lipids (mainly dipalmitoylphosphatidylcholine or DPPC) and ∼10 wt% surfactant proteins (SP-A, -B, -C, and -D), adsorb to an air-alveolar fluid interface and then lower its surface tension down to near zero during expiration. Intratracheal instillation of exogenous LS preparations can effectively compensate for surfactant deficiency in premature infants with respiratory distress syndrome (RDS). Surfacten® (Mitsubishi Tanabe Pharma Corporation, Osaka, Japan), a modified bovine lung extract and an effective surfactant replacement in treatment for RDS patients, is supplemented with DPPC, palmitic acid, and tripalmitin. For the premature infants suffering from RDS, instillation of Surfacten® leads to a dramatic improvement in lung function and compliance. Herein, the author reviews potential use of newly designed preparations containing a mimicking peptide of SP-B and also introduces the current research on the preparations incorporated with partially fluorinated amphiphiles to improve their efficacy. PMID:22790027

  4. 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...... 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...... or restoration of the structural and functional integrity of the remaining intestine with significant intestinotrophic and proabsorptive effects, facilitating a reduction in diarrhea and an equivalent reduction in the need for PS in patients with short bowel syndrome and intestinal failure....

  5. Gut hormones, and short bowel syndrome: The enigmatic role of glucagon-like peptide-2 in the regulation of intestinal adaptation

    Institute of Scientific and Technical Information of China (English)

    GR Martin; PL Beck; DL Sigalet

    2006-01-01

    Short bowel syndrome (SBS) refers to the malabsorption of nutrients, water, and essential vitamins as a result of disease or surgical removal of parts of the small intestine. The most common reasons for removing part of the small intestine are due to surgical intervention for the treatment of either Crohn's disease or necrotizing enterocolitis. Intestinal adaptation following resection may take weeks to months to be achieved, thus nutritional support requires a variety of therapeutic measures, which include parenteral nutrition. Improper nutrition management can leave the SBS patient malnourished and/or dehydrated, which can be life threatening. The development of therapeutic strategies that reduce both the complications and medical costs associated with SBS/long-term parenteral nutrition while enhancing the intestinal adaptive response would be valuable.Currently, therapeutic options available for the treatment of SBS are limited. There are many potential stimulators of intestinal adaptation including peptide hormones, growth factors, and neuronally-derived components. Glucagon-like peptide-2 (GLP-2) is one potential treatment for gastrointestinal disorders associated with insufficient mucosal function. A significant body of evidence demonstrates that GLP-2is atrophic hormone that plays an important role in controlling intestinal adaptation. Recent data from clinical trials demonstrate that GLP-2 is safe, well-tolerated, and promotes intestinal growth in SBS patients. However,the mechanism of action and the localization of the glucagon-like peptide-2 receptor (GLP-2R) remains an enigma. This review summarizes the role of a number of mucosal-derived factors that might be involved with intestinal adaptation processes; however, this discussion primarily examines the physiology, mechanism of action,and utility of GLP-2 in the regulation of intestinal mucosal growth.

  6. Short Stat5-interacting peptide derived from phospholipase C-β3 inhibits hematopoietic cell proliferation and myeloid differentiation.

    Directory of Open Access Journals (Sweden)

    Hiroki Yasudo

    Full Text Available Constitutive activation of the transcription factor Stat5 in hematopoietic stem/progenitor cells leads to various hematopoietic malignancies including myeloproliferative neoplasm (MPN. Our recent study found that phospholipase C (PLC-β3 is a novel tumor suppressor involved in MPN, lymphoma and other tumors. Stat5 activity is negatively regulated by the SH2 domain-containing protein phosphatase SHP-1 in a PLC-β3-dependent manner. PLC-β3 can form the multimolecular SPS complex together with SHP-1 and Stat5. The close physical proximity of SHP-1 and Stat5 brought about by interacting with the C-terminal segment of PLC-β3 (PLC-β3-CT accelerates SHP-1-mediated dephosphorylation of Stat5. Here we identify the minimal sequences within PLC-β3-CT required for its tumor suppressor function. Two of the three Stat5-binding noncontiguous regions, one of which also binds SHP-1, substantially inhibited in vitro proliferation of Ba/F3 cells. Surprisingly, an 11-residue Stat5-binding peptide (residues 988-998 suppressed Stat5 activity in Ba/F3 cells and in vivo proliferation and myeloid differentiation of hematopoietic stem/progenitor cells. Therefore, this study further defines PLC-β3-CT as the Stat5- and SHP-1-binding domain by identifying minimal functional sequences of PLC-β3 for its tumor suppressor function and implies their potential utility in the control of hematopoietic malignancies.

  7. Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies.

    Science.gov (United States)

    Hancock, Robert E W; Sahl, Hans-Georg

    2006-12-01

    Short cationic amphiphilic peptides with antimicrobial and/or immunomodulatory activities are present in virtually every life form, as an important component of (innate) immune defenses. These host-defense peptides provide a template for two separate classes of antimicrobial drugs. Direct-acting antimicrobial host-defense peptides can be rapid-acting and potent, and possess an unusually broad spectrum of activity; consequently, they have prospects as new antibiotics, although clinical trials to date have shown efficacy only as topical agents. But for these compounds to fulfill their therapeutic promise and overcome clinical setbacks, further work is needed to understand their mechanisms of action and reduce the potential for unwanted toxicity, to make them more resistant to protease degradation and improve serum half-life, as well as to devise means of manufacturing them on a large scale in a consistent and cost-effective manner. In contrast, the role of cationic host-defense peptides in modulating the innate immune response and boosting infection-resolving immunity while dampening potentially harmful pro-inflammatory (septic) responses gives these peptides the potential to become an entirely new therapeutic approach against bacterial infections.

  8. 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.

  9. Nanostructured assemblies from amphiphilic ABC multiblock polymers

    Science.gov (United States)

    Hillmyer, Marc A.

    2012-02-01

    Amphiphilic AB diblock copolymers containing a water compatible segment can self-assemble in aqueous media to give supramolecular structures that include simple spherical micelles and macromolecular vesicles termed polymersomes. Amphiphilic ABA triblocks with hydrophobic end blocks can adopt analogous structures but can also form gels at high polymer concentrations. The structural and chemical diversity demonstrated in block copolymer micelles and gels makes them attractive for applications ranging from drug delivery to personal care products to nanoreactors. The inclusion of a third block in amphiphilic ABC triblock systems can lead to a much wider array of self-assembled structures that depend not only on composition but also on block sequence, architecture and incompatibility considerations. I will present our recent efforts on tuning micelle and gel structure and behavior using controlled architecture ABC triblocks. The combination of diverse polymer segments into a single macromolecule is a powerful method for development of self-assembled structures with both new form and new function.

  10. Prediction on amphiphilicity of hypocrellin derivatives

    Institute of Scientific and Technical Information of China (English)

    谢杰; 马江华; 赵井泉

    2002-01-01

    Hypocrellins are most suitable for photodynamic therapy (PDT) of the diseases occurring in the superficial layer, such as microvascular diseases, because of their special absorption spectral properties. However, hypocrellins and most of their derivatives are basically lipophilic, while the hydrophilic derivatives lose the PDT activity in vivo. Therefore, the key problem for practical application of PDT of microvascular diseases focuses on finding the derivatives which possess optimized amphiphilicity. Herein, we developed a theoretical method to estimate the amphi-philicity of a molecule by the calculated average polarity. Compared with the experimentally measured results, the method is proved to be applicable. Based on the computation and available experimental results, it can be concluded that the derivative must have the polarities around C.22 for optimized amphiphilicity.

  11. Prediction on amphiphilicity of hypocrellin derivatives

    Institute of Scientific and Technical Information of China (English)

    谢杰; 马江华; 赵井泉

    2002-01-01

    Hypocrellins are most suitable for photodynamic therapy (PDT) of the diseases occurring in the superficial layer, such as microvascular diseases, because of their special absorption spectral properties. However, hypocrellins and most of their derivatives are basically lipophilic, while the hydrophilic derivatives lose the PDT activity in vivo. Therefore, the key problem for practical application of PDT of microvascular diseases focuses on finding the derivatives which possess optimized amphiphilicity. Herein, we developed a theoretical method to estimate the amphiphilicity of a molecule by the calculated average polarity. Compared with the experimentally measured results, the method is proved to be applicable. Based on the computation and available experimental results, it can be concluded that the derivative must have the polarities around 0.22 for optimized amphiphilicity.

  12. 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 en...

  13. Quality of life in patients with short bowel syndrome treated with the new glucagon-like peptide-2 analogue teduglutide--analyses from a randomised, placebo-controlled study

    DEFF Research Database (Denmark)

    Jeppesen, P B; Pertkiewicz, M; Forbes, A;

    2013-01-01

    Short bowel syndrome (SBS)-intestinal failure (IF) patients have impaired quality of life (QoL) and suffer from the burden of malabsorption and parenteral support (PS). A phase III study demonstrated that treatment with teduglutide, a glucagon-like peptide 2 analogue, reduces PS volumes by 32% wh...

  14. Ratiometric fluorescence sensing of sugars via a reversible disassembly and assembly of the peptide aggregates mediated by sugars.

    Science.gov (United States)

    Neupane, Lok Nath; Han, Song Yee; Lee, Keun-Hyeung

    2014-06-01

    An amphiphilic dipeptide (1) bearing pyrene and phenylboronic acid was demonstrated as a unique example of a ratiometric sensing system for sugars by reversibly converting the peptide aggregates into the monomer form of the complex with sugars in aqueous solutions.

  15. Interactions of Bio-Inspired Membranes with Peptides and Peptide-Mimetic Nanoparticles

    Directory of Open Access Journals (Sweden)

    Michael Sebastiano

    2015-08-01

    Full Text Available Via Dissipative Particle Dynamics (DPD and implicit solvent coarse-grained (CG Molecular Dynamics (MD we examine the interaction of an amphiphilic cell-penetrating peptide PMLKE and its synthetic counterpart with a bio-inspired membrane. We use the DPD technique to investigate the interaction of peptide-mimetic nanoparticles, or nanopins, with a three-component membrane. The CG MD approach is used to investigate the interaction of a cell-penetrating peptide PMLKE with single-component membrane. We observe the spontaneous binding and subsequent insertion of peptide and nanopin in the membrane by using CG MD and DPD approaches, respectively. In addition, we find that the insertion of peptide and nanopins is mainly driven by the favorable enthalpic interactions between the hydrophobic components of the peptide, or nanopin, and the membrane. Our study provides insights into the mechanism underlying the interactions of amphiphilic peptide and peptide-mimetic nanoparticles with a membrane. The result of this study can be used to guide the functional integration of peptide and peptide-mimetic nanoparticles with a cell membrane.

  16. Designing new symmetrical facial oligothiophene amphiphiles

    NARCIS (Netherlands)

    Janeliunas, Dainius; Eelkema, Rienk; Nieto-Ortega, Belén; Ramírez Aguilar, Francisco J; López Navarrete, Juan T; van der Mee, Lars; Stuart, Marc C A; Casado, Juan; van Esch, Jan H

    2013-01-01

    In this study we designed a new class of symmetrical facial oligothiophene amphiphiles, which could be obtained in fewer steps than for previously reported analogues, but still possess the specific substituent sequence to control their backbone curvature. This novel design allows the late-stage intr

  17. 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 dynam...

  18. Synthesis and Self-Assembly of a Mikto-Arm Star Dual Drug Amphiphile Containing both Paclitaxel and Camptothecin

    OpenAIRE

    Cheetham, A.G.; Zhang, P.; Lin, Y.-A; Lin, R; Cui, H

    2014-01-01

    Self-assembly of anticancer therapeutics into discrete nanostructures provides an innovative way to develop a self-delivering nanomedicine with a high, quantitative drug loading. We report here the synthesis and assembly of a mikto-arm star dual drug amphiphile (DA) containing both a bulky paclitaxel (PTX) and a planar camptothecin (CPT). The two anti-cancer drugs of interest were stochastically conjugated to a β-sheet forming peptide (Sup35) and under physiologically-relevant conditions the ...

  19. Screening and assessment of short peptide with skin whitening efficacy%具有透皮美白功效的短肽筛选和评价研究

    Institute of Scientific and Technical Information of China (English)

    刘荣; 孙建宁; 郭亚健; 齐宁宁

    2011-01-01

    筛选具有透皮性能的短肽并评价其美白功效.方法:采用噬菌体表面展示技术透Wistar大鼠腹部皮肤筛选透皮短肽,以L-多巴为底物,检测短肽对酪氨酸酶活性的抑制作用.体外培养B16小鼠黑素瘤细胞,检测短肽对细胞内黑素生成的抑制作用,以豚鼠为实验对象,考察短肽对豚鼠皮肤内黑素的生成抑制作用.结果:通过噬菌体表面展示技术筛选出4条透皮短肽,其中一条氨基酸序列为ACSSQPPYACG的短肽P1,其对酪氨酸酶活性的半数抑制浓度IC50值为25.64μg/ml,能够明显抑制B16小鼠黑素瘤细胞和豚鼠皮肤内黑素生成.结论:成功建立了利用噬菌体表面展示技术筛选具有美白功效短肽的方法,为美白成分的筛选提供了新的途径.%Objective To screen short peptide with transdermal property and assess its skin whitening efficacy. Methods Transdermal short peptide was screened with Phage display technique, and its inhibition on Tyrosinase was measured with L-Dopa as substrate. The inhibition of the short peptide on the melanogenesis was assessed with B16 melanoma cells and guinea pig, respectively. Results Among four short peptides screened, one short peptide named P1 (Sequence ACSSQPPYACG) could inhibit the Tyrosinase activity, and the half maximal inhibitory concentration (IC50) was 25.64vig/ml.Furthermore, P1 could inhibit the melanogenesis of B16 melanoma cells and guinea pig effectively. Conclusions Transdermal short peptides were screened with phage display technique successfully and proven to be skin whitening efficacious, which provide a new screening way for new whitening ingredients.

  20. Short communication: Measuring the angiotensin-converting enzyme inhibitory activity of an 8-amino acid (8mer) fragment of the C12 antihypertensive peptide.

    Science.gov (United States)

    Paul, Moushumi; Phillips, John G; Renye, John A

    2016-05-01

    An 8-AA (8mer) fragment (PFPEVFGK) of a known antihypertensive peptide derived from bovine αS1-casein (C12 antihypertensive peptide) was synthesized by microwave-assisted solid-phase peptide synthesis and purified by reverse phase HPLC. Its ability to inhibit angiotensin-converting enzyme (ACE) was assessed and compared with that of the parent 12mer peptide (FFVAPFPEVFGK) to determine the effect of truncating the sequence on overall hypotensive activity. The activity of the truncated 8mer peptide was found to be almost 1.5 times less active than that of the 12mer, with ACE-inhibiting IC50 (half-maximal inhibitory concentration) values of 108 and 69μM, for the 8mer and 12mer, respectively. Although the 8mer peptide is less active than the original 12mer peptide, its overall activity is comparable to activities reported for other small proteins that elicit physiological responses within humans. These results suggest that microbial degradation of the 12mer peptide would not result in a complete loss of antihypertensive activity if used to supplement fermented foods and that the stable 8mer peptide could have potential as a blood pressure-lowering agent for use in functional foods. PMID:26971162

  1. Short communication: Measuring the angiotensin-converting enzyme inhibitory activity of an 8-amino acid (8mer) fragment of the C12 antihypertensive peptide.

    Science.gov (United States)

    Paul, Moushumi; Phillips, John G; Renye, John A

    2016-05-01

    An 8-AA (8mer) fragment (PFPEVFGK) of a known antihypertensive peptide derived from bovine αS1-casein (C12 antihypertensive peptide) was synthesized by microwave-assisted solid-phase peptide synthesis and purified by reverse phase HPLC. Its ability to inhibit angiotensin-converting enzyme (ACE) was assessed and compared with that of the parent 12mer peptide (FFVAPFPEVFGK) to determine the effect of truncating the sequence on overall hypotensive activity. The activity of the truncated 8mer peptide was found to be almost 1.5 times less active than that of the 12mer, with ACE-inhibiting IC50 (half-maximal inhibitory concentration) values of 108 and 69μM, for the 8mer and 12mer, respectively. Although the 8mer peptide is less active than the original 12mer peptide, its overall activity is comparable to activities reported for other small proteins that elicit physiological responses within humans. These results suggest that microbial degradation of the 12mer peptide would not result in a complete loss of antihypertensive activity if used to supplement fermented foods and that the stable 8mer peptide could have potential as a blood pressure-lowering agent for use in functional foods.

  2. 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, this s...... study evaluated the acute effects of continuous intravenous administration of glucagon-like peptide (GLP) 1 and 2, alone or in combination, on gastrointestinal function in SBS patients....

  3. Foams Stabilized by Tricationic Amphiphilic Surfactants

    OpenAIRE

    Heerschap, Seth; Marafino, John N.; McKenna, Kristin; Caran, Kevin L.; Feitosa, Klebert

    2015-01-01

    The unique surface properties of amphiphilic molecules have made them widely used in applications where foaming, emulsifying or coating processes are needed. Novel surfactant architectures with multi-cephalic and multi-tailed molecules have reportedly enhanced their anti-bacterial activity in connection with tail length and the nature of the head group, but their ability to produce and stabilize foam is mostly unknown. Here we report on experiments with tris-cationic, triple-headed, double- a...

  4. Amphiphilic Fullerenes for Biomedical and Optoelectronical Applications

    OpenAIRE

    Witte, Patrick

    2009-01-01

    Fullerenes have an enormous potential in applications to physics and biology. Specifically [60]fullerene with its unique electronic, optical and structural properties has attracted considerable attention for its application in biomedical materials and optoelectronic devices. In this context the selective functionalization of C60, which allows to combine the parent properties with new attributes like water-solubility or amphiphilicity is still a challenging topic for the synthetic chemist. In ...

  5. Prebiotic Lipidic Amphiphiles and Condensing Agents on the Early Earth

    OpenAIRE

    Michele Fiore; Peter Strazewski

    2016-01-01

    It is still uncertain how the first minimal cellular systems evolved to the complexity required for life to begin, but it is obvious that the role of amphiphilic compounds in the origin of life is one of huge relevance. Over the last four decades a number of studies have demonstrated how amphiphilic molecules can be synthesized under plausibly prebiotic conditions. The majority of these experiments also gave evidence for the ability of so formed amphiphiles to assemble in closed membranes of ...

  6. Nanocapsules templated on liquid cores stabilized by graft amphiphilic polyelectrolytes

    Science.gov (United States)

    Szafraniec, Joanna; Janik, Małgorzata; Odrobińska, Joanna; Zapotoczny, Szczepan

    2015-03-01

    A surfactant-free method of preparation of nanocapsules templated on liquid cores using amphiphilic graft polyelectrolytes was developed. A model photoactive copolymer, poly(sodium 2-acrylamido-2-methyl-1-propanesulfonate) with grafted poly(vinylnaphthalene) chains (PAMPS-graft-PVN) was used to stabilize toluene droplets in an aqueous emulsion. The macromolecules, due to their amphiphilic character and the presence of strong ionic groups, tend to undergo intramolecular aggregation in water but at the water-oil interface less compact conformation is preferred with PVN grafts anchoring in the oil phase and the charged PAMPS main chains residing in the aqueous phase, thus stabilizing the nanoemulsion droplets. Formation of such nanocapsules was confirmed by dynamic light scattering measurements as well as SEM and cryo-TEM imaging. Grafting density and content of the chromophores in the graft copolymers were varied in order to achieve high stability of the coated nanodroplets. It was shown that the capsules are better stabilized by the copolymers with many short hydrophobic grafts than with fewer but longer ones. Use of photoactive polyelectrolytes enabled spectroscopic investigation of the relationship between conformation of the macromolecules and stabilization of the oil-core nanocapsules. Long-term stability of the nanocapsules was achieved and further increased by multilayer shell formation using polyelectrolytes deposited via the layer-by-layer approach. The obtained capsules served as efficient nanocontainers for a hydrophobic fluorescent probe. The proposed strategy of nanocapsule preparation may be easily extended to biologically relevant polymers and applied to fabricate liquid core nanodelivery systems without the need of using low molecular weight additives which may have adverse effects in numerous biomedical applications.A surfactant-free method of preparation of nanocapsules templated on liquid cores using amphiphilic graft polyelectrolytes was developed

  7. Function of Amphiphilic Biomolecular Machines: Elastic Protein-based Polymers

    Science.gov (United States)

    Urry, Dan W.

    2000-03-01

    Elastic protein-based polymers function as biomolecular machines due to inverse temperature transitions of hydrophobic folding and assembly. The transitions occur either on raising the temperature from below to above the transition temperature, Tt, or on isothermally lowering Tt from above to below an operating temperature. The inverse temperature transition involves a decrease in entropy of the polymer component of the system on raising the temperature and a larger increase in solvent entropy on hydrophobic association. Tt depends on the quantity of hydrophobic hydration that undergoes transition to bulk water. Designed amphiphilic polymers perform free energy transductions involving the intensive variables of mechanical force, pressure, temperature, chemical potential, electrochemical potential and electromagnetic radiation and define a set of five axioms for their function as machines. The physical basis for these diverse energy conversions is competition for hydration between apolar (hydrophobic) and polar (e.g., charged) moieties. The effectiveness of these Tt-type entropic elastic protein-based machines is due to repeating peptide sequences that form regular, dynamic repeating structures and exhibit damping of backbone torsional oscillations on extension.

  8. Amphiphilic, hydrophilic, or hydrophobic synthetic bacteriochlorins in biohybrid light-harvesting architectures: consideration of molecular designs.

    Science.gov (United States)

    Jiang, Jianbing; Reddy, Kanumuri Ramesh; Pavan, M Phani; Lubian, Elisa; Harris, Michelle A; Jiao, Jieying; Niedzwiedzki, Dariusz M; Kirmaier, Christine; Parkes-Loach, Pamela S; Loach, Paul A; Bocian, David F; Holten, Dewey; Lindsey, Jonathan S

    2014-11-01

    Biohybrid light-harvesting architectures can be constructed that employ native-like bacterial photosynthetic antenna peptides as a scaffold to which synthetic chromophores are attached to augment overall spectral coverage. Synthetic bacteriochlorins are attractive to enhance capture of solar radiation in the photon-rich near-infrared spectral region. The effect of the polarity of the bacteriochlorin substituents on the antenna self-assembly process was explored by the preparation of a bacteriochlorin-peptide conjugate using a synthetic amphiphilic bacteriochlorin (B1) to complement prior studies using hydrophilic (B2, four carboxylic acids) or hydrophobic (B3) bacteriochlorins. The amphiphilic bioconjugatable bacteriochlorin B1 with a polar ammonium-terminated tail was synthesized by sequential Pd-mediated reactions of a 3,13-dibromo-5-methoxybacteriochlorin. Each bacteriochlorin bears a maleimido-terminated tether for attachment to a cysteine-containing analog of the Rhodobacter sphaeroides antenna β-peptide to give conjugates β-B1, β-B2, and β-B3. Given the hydrophobic nature of the β-peptide, the polarity of B1 and B2 facilitated purification of the respective conjugate compared to the hydrophobic B3. Bacteriochlorophyll a (BChl a) associates with each conjugate in aqueous micellar media to form a dyad containing two β-peptides, two covalently attached synthetic bacteriochlorins, and a datively bonded BChl-a pair, albeit to a limited extent for β-B2. The reversible assembly/disassembly of dyad (β-B2/BChl)2 was examined in aqueous detergent (octyl glucoside) solution by temperature variation (15-35 °C). The energy-transfer efficiency from the synthetic bacteriochlorin to the BChl-a dimer was found to be 0.85 for (β-B1/BChl)2, 0.40 for (β-B2/BChl)2, and 0.85 for (β-B3/BChl)2. Thus, in terms of handling, assembly and energy-transfer efficiency taken together, the amphiphilic design examined herein is more attractive than the prior hydrophilic or

  9. Collagen-like antimicrobial peptides.

    Science.gov (United States)

    Masuda, Ryo; Kudo, Masakazu; Dazai, Yui; Mima, Takehiko; Koide, Takaki

    2016-11-01

    Combinatorial library composed of rigid rod-like peptides with a triple-helical scaffold was constructed. The component peptides were designed to have various combinations of basic and neutral (or hydrophobic) amino acid residues based on collagen-like (Gly-Pro-Yaa)-repeating sequences, inspired from the basic and amphiphilic nature of naturally occurring antimicrobial peptides. Screening of the peptide pools resulted in identification of antimicrobial peptides. A structure-activity relationship study revealed that the position of Arg-cluster at N-terminus and cystine knots at C-terminus in the triple helix significantly contributed to the antimicrobial activity. The most potent peptide RO-A showed activity against Gram-negative Escherichia coli and Gram-positive Bacillus subtilis. In addition, Escherichia coli exposed to RO-A resulted in abnormal elongation of the cells. RO-A was also shown to have remarkable stability in human serum and low cytotoxicity to mammalian cells. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 453-459, 2016. PMID:27271210

  10. 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.)

  11. Water Diffusion Dependence on Amphiphilic Block Design in (Amphiphilic-Hydrophobic) Diblock Copolymer Membranes.

    Science.gov (United States)

    Dorenbos, Gert

    2016-06-30

    Polyelectrolyte membranes (PEMs) are applied in polyelectrolyte fuel cells (PEFC). The proton conductive pathways within PEMs are provided by nanometer-sized water containing pores. Large-scale application of PEFC requires the production of low-cost membranes with high proton conductivity and therefore good connected pore networks. Pore network formation within four alternative model diblock (hydrophobic_amphiphilic) copolymers in the presence of water is studied by dissipative particle dynamics. Each hydrophobic block contains 50 consecutively connected hydrophobic (A) fragments, and amphiphilic blocks contain 40 hydrophobic A beads and 10 hydrophilic C beads. For one amphiphilic block the C beads are distributed uniformly along the backbone. For the other architectures C beads are located at the end of the side chains attached at regular intervals along the backbone. Water diffusion through the pores is modeled by Monte Carlo tracer diffusion through mapped morphologies. Diffusion is highest for the grafted architectures and increases with increase of length of the side chains. A consistent picture emerges in which diffusion strongly increases with the value of ⟨Nbond⟩ within the amphiphilic block, where ⟨Nbond⟩ is the average number of bonds between hydrophobic A beads and the nearest C bead. PMID:27266679

  12. Glucose-neopentyl glycol (GNG) amphiphiles for membrane protein study

    DEFF Research Database (Denmark)

    Chae, Pil Seok; Rana, Rohini R; Gotfryd, Kamil;

    2013-01-01

    The development of a new class of surfactants for membrane protein manipulation, "GNG amphiphiles", is reported. These amphiphiles display promising behavior for membrane proteins, as demonstrated recently by the high resolution structure of a sodium-pumping pyrophosphatase reported by Kellosalo et...

  13. Amphiphile nanoarchitectonics: from basic physical chemistry to advanced applications.

    Science.gov (United States)

    Ramanathan, Muruganathan; Shrestha, Lok Kumar; Mori, Taizo; Ji, Qingmin; Hill, Jonathan P; Ariga, Katsuhiko

    2013-07-14

    Amphiphiles, either synthetic or natural, are structurally simple molecules with the unprecedented capacity to self-assemble into complex, hierarchical geometries in nanospace. Effective self-assembly processes of amphiphiles are often used to mimic biological systems, such as assembly of lipids and proteins, which has paved a way for bottom-up nanotechnology with bio-like advanced functions. Recent developments in nanostructure formation combine simple processes of assembly with the more advanced concept of nanoarchitectonics. In this perspective, we summarize research on self-assembly of amphiphilic molecules such as lipids, surfactants or block copolymers that are a focus of interest for many colloid, polymer, and materials scientists and which have become increasingly important in emerging nanotechnology and practical applications, latter of which are often accomplished by amphiphile-like polymers. Because the fundamental science of amphiphiles was initially developed for their solution assembly then transferred to assemblies on surfaces as a development of nanotechnological techniques, this perspective attempts to mirror this development by introducing solution systems and progressing to interfacial systems, which are roughly categorized as (i) basic properties of amphiphiles, (ii) self-assembly of amphiphiles in bulk phases, (iii) assembly on static surfaces, (iv) assembly at dynamic interfaces, and (v) advanced topics from simulation to application. This progression also represents the evolution of amphiphile science and technology from simple assemblies to advanced assemblies to nanoarchitectonics.

  14. Incorporation of Amphiphilic Cyclodextrins into Liposomes as Artificial Receptor Units

    NARCIS (Netherlands)

    Kauscher, Ulrike; Stuart, Marc C. A.; Druecker, Patrick; Galla, Hans-Joachim; Ravoo, Bart Jan

    2013-01-01

    In this article, we describe the introduction of amphiphilic beta-cyclodextrins into liposomes to act as artificial receptor units. Using dynamic light scattering, dye encapsulation, and cryogenic transmission electron microscopy, we show that amphiphilic beta-cyclodextrins can be mixed in any propo

  15. Absence of in vitro innate immunomodulation by insect-derived short proline-rich antimicrobial peptides points to direct antibacterial action in vivo.

    Science.gov (United States)

    Fritsche, Stefanie; Knappe, Daniel; Berthold, Nicole; von Buttlar, Heiner; Hoffmann, Ralf; Alber, Gottfried

    2012-10-01

    Some antimicrobial peptides (AMPs) have been described to exert immunomodulatory effects, which may contribute to their in vivo antibacterial activity. Very recently, we could show that novel oncocin and apidaecin derivatives are potently antibacterially active in vivo. Therefore, we studied oncocin and apidaecin derivatives for their effects on murine dendritic cells (DC) and macrophages and compared them with well-known immunomodulatory activities of murine cathelicidin-related antimicrobial peptide (CRAMP). To characterize the immunomodulatory activity of the peptides on key cells of the innate immune system, we stimulated murine DC and macrophages with the oncocin and apidaecin derivatives alone, or in combination with lipopolysaccharide (LPS). We analyzed the secretion of pro-inflammatory cytokines, the expression of surface activation markers, and the chemotactic activity of the AMPs. In contrast to LPS, none of the oncocin and apidaecin derivatives alone has an influence on cytokine or surface marker expression by DC and macrophages. Furthermore, the tested oncocin and apidaecin derivatives do not modulate the immune response after LPS stimulation, whereas CRAMP shows a reduction of the LPS-mediated immune response as expected. All peptides tested are not chemotactic for DC. Together, lack of in vitro immunomodulatory effects by oncocin and apidaecin derivatives on key cells of the innate murine immune system suggests that their potent in vivo antibacterial activity relies on a direct antibacterial effect. This will simplify further pharmaceutical investigation and development of insect peptides as therapeutic compounds against bacterial infections.

  16. Mitochondria-acting hexokinase II peptides carried by short-length carbon nanotubes with increased cellular uptake, endosomal evasion, and enhanced bioactivity against cancer cells

    Science.gov (United States)

    Yoong, Sia Lee; Lau, Wei Liang; Liu, Ang Yu; Prendergast, D'arcy; Ho, Han Kiat; Yu, Victor Chun Kong; Lee, Chengkuo; Ang, Wee Han; Pastorin, Giorgia

    2015-08-01

    Type II hexokinase (HKII) has emerged as a viable therapeutic target due to its involvement in metabolic reprogramming and also apoptosis prevention. The peptide derived from the fifteen amino acid sequence in the HKII N-terminal region [HKII(pep)] can compete with endogenous proteins for binding on mitochondria and trigger apoptosis. However, this peptide is not cell-permeable. In this study, multi-walled carbon nanotubes (MWCNTs) were used to effectively deliver HKII(pep) across cellular barriers without compromising their bioactivity. The peptide was conjugated on either oxidized MWCNTs or 2,2'-(ethylenedioxy)bis(ethylamine)-functionalized MWCNTs, yielding MWCNT-HKII(pep) and MWCNT-TEG-HKII(pep), respectively. Both conjugates were shown to be internalized by breast cancer MCF-7 cells using confocal microscopy. Moreover, these nanoconjugates seemed to have escaped from endosomes and be in the vicinity of mitochondria. The WST-1 cytotoxicity assay conducted on MCF-7 and colon carcinoma HCT116 cells revealed that MWCNT-peptide conjugates were significantly more effective in curbing cancer cell growth compared to a commercially available cell permeable HKII fusion peptide. In addition, both nanoconjugates displayed an enhanced ability in eliciting apoptosis and depleting the ATP level in HCT116 cells compared to the mere HKII peptide. Importantly, hexokinase II release from mitochondria was demonstrated in MWCNT-HKII(pep) and MWCNT-TEG-HKII(pep) treated cells, highlighting that the structure and bioactivity of HKII(pep) were not compromised after covalent conjugation to MWCNTs.Type II hexokinase (HKII) has emerged as a viable therapeutic target due to its involvement in metabolic reprogramming and also apoptosis prevention. The peptide derived from the fifteen amino acid sequence in the HKII N-terminal region [HKII(pep)] can compete with endogenous proteins for binding on mitochondria and trigger apoptosis. However, this peptide is not cell-permeable. In this study

  17. The Behavior of Amphiphile at Oil-Water Interface by Monte Carlo Simulation

    Institute of Scientific and Technical Information of China (English)

    潘海华; 李啸风; 李浩然; 刘迪霞; 韩世钧

    2003-01-01

    A novel simple two-dimensional square-lattice model of amphiphile at oil-water interface is developed,in which oil and water act as solvent and occupy empty sites and amphiphile occupies chains of sites. In this model, the oil-water interface is fixed, And amphiphile molecules will be enriched at the oil-water interface. The interfacial concentration of amphiphile calculated by Monte Carlo method shows that it is easier for the hydrophilic-hydrophobic balanced amphiphile to stay at the interface. And the adsorption of amphiphile increases with the increase of amphiphile concentration and the decrease with temperature.

  18. 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...

  19. Amphiphile nanoarchitectonics: from basic physical chemistry to advanced applications

    Energy Technology Data Exchange (ETDEWEB)

    Ramanathan, Nathan Muruganathan [ORNL; Shrestha, Lok Kumar [International Center for Materials Nanoarchitectonics (MANA); Mori, Taizo [International Center for Materials Nanoarchitectonics (MANA); Ji, Dr. Qingmin [National Institute for Materials Science, Tsukuba, Japan; Hill, Dr. Jonathan P [National Institute for Materials Science, Tsukuba, Japan; Ariga, Katsuhiko [National Institute for Materials Science, Tsukuba, Japan

    2013-01-01

    Amphiphiles, either synthetic or natural, are structurally simple molecules with the unprecedented capacity to self-assemble into complex, hierarchical geometries in nanospace. Effective self-assembly processes of amphiphiles are often used to mimic biological systems, such as, assembly of lipids and proteins, which has paved a way for bottom-up nanotechnology with bio-like advanced functions. Recent developments on nanostructure formation combine simple processes of assembly with the more advanced concept of nanoarchitectonics. In this pespective, we summarize research on self-assembly of amphiphilic molecules such as lipids, surfactants or block copolymers that are a focus of interest for many colloid, polymer, and materials scientists and which have become increasingly important in emerging nanotechnology. Because the fundamental science of amphiphiles was initially developed for their solution assembly then transferred to assemblies on surfaces as a development of nanotechnological technique, this perspective attempts to mirro this development by introducing solution systems and progressing to interfacial systems, which are roughly categorized as (i) basic properties of amphiphiles, (ii) self-assembly of amphiphiles in bulk phases, (iii) assembly on static surfaces, (iv) assembly at dynamic interfaces, and (v) advanced topics from simulation to application. This progression also represents the evolution of amphiphile science and technology from simple assemblies to advanced assemblies to nanoarchitectonics.

  20. 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.

  1. Recent development of peptide self-assembly

    Institute of Scientific and Technical Information of China (English)

    Xiubo Zhao; Fang Pan; Jian R. Lu

    2008-01-01

    Amino acids are the building blocks to build peptides and proteins. Recent development in peptide synthesis has however enabled us to mimic this natural process by preparing various long and short peptides possessing different conformations and biological functions. The self-assembly of short designed peptides into molecular nanostructures is becoming a growing interest in nanobiotechnology. Self-assembled peptides exhibit several attractive features for applications in tissue regeneration, drug delivery, biological surface engineering as well as in food science, cosmetic industry and antibiotics. The aim of this review is to introduce the readers to a number of representative studies on peptide self-assembly.

  2. Membrane Thinning and Thickening Induced by Membrane-Active Amphipathic Peptides.

    Science.gov (United States)

    Grage, Stephan L; Afonin, Sergii; Kara, Sezgin; Buth, Gernot; Ulrich, Anne S

    2016-01-01

    Membrane thinning has been discussed as a fundamental mechanism by which antimicrobial peptides can perturb cellular membranes. To understand which factors play a role in this process, we compared several amphipathic peptides with different structures, sizes and functions in their influence on the lipid bilayer thickness. PGLa and magainin 2 from X. laevis were studied as typical representatives of antimicrobial cationic amphipathic α-helices. A 1:1 mixture of these peptides, which is known to possess synergistically enhanced activity, allowed us to evaluate whether and how this synergistic interaction correlates with changes in membrane thickness. Other systems investigated here include the α-helical stress-response peptide TisB from E. coli (which forms membrane-spanning dimers), as well as gramicidin S from A. migulanus (a natural antibiotic), and BP100 (designer-made antimicrobial and cell penetrating peptide). The latter two are very short, with a circular β-pleated and a compact α-helical structure, respectively. Solid-state (2)H-NMR and grazing incidence small angle X-ray scattering (GISAXS) on oriented phospholipid bilayers were used as complementary techniques to access the hydrophobic thickness as well as the bilayer-bilayer repeat distance including the water layer in between. This way, we found that magainin 2, gramicidin S, and BP100 induced membrane thinning, as expected for amphiphilic peptides residing in the polar/apolar interface of the bilayer. PGLa, on the other hand, decreased the hydrophobic thickness only at very high peptide:lipid ratios, and did not change the bilayer-bilayer repeat distance. TisB even caused an increase in the hydrophobic thickness and repeat distance. When reconstituted as a mixture, PGLa and magainin 2 showed a moderate thinning effect which was less than that of magainin 2 alone, hence their synergistically enhanced activity does not seem to correlate with a modulation of membrane thickness. Overall, the absence of

  3. Neomycin-phenolic conjugates: polycationic amphiphiles with broad-spectrum antibacterial activity, low hemolytic activity and weak serum protein binding.

    Science.gov (United States)

    Findlay, Brandon; Zhanel, George G; Schweizer, Frank

    2012-02-15

    Here we present a proof-of-concept study, combining two known antimicrobial agents into a hybrid structure in order to develop an emergent cationic detergent-like interaction with the bacterial membrane. Six amphiphilic conjugates were prepared by copper (I)-catalyzed 1,3-dipolar cycloaddition between a neomycin B-derived azide and three alkyne-modified phenolic disinfectants. Three conjugates displayed good activity against a variety of clinically relevant Gram positive and Gram negative bacteria, including MRSA, without the high level of hemolysis or strong binding to serum proteins commonly observed with other cationic antimicrobial peptides and detergents.

  4. Comparison of facially amphiphilic versus segregated monomers in the design of antibacterial copolymers.

    Science.gov (United States)

    Gabriel, Gregory J; Maegerlein, Janet A; Nelson, Christopher F; Dabkowski, Jeffrey M; Eren, Tarik; Nüsslein, Klaus; Tew, Gregory N

    2009-01-01

    A direct comparison of two strategies for designing antimicrobial polymers is presented. Previously, we published several reports on the use of facially amphiphilic (FA) monomers which led to polynorbornenes with excellent antimicrobial activities and selectivities. Our polymers obtained by copolymerization of structurally similar segregated monomers, in which cationic and non-polar moieties reside on separate repeat units, led to polymers with less pronounced activities. A wide range of polymer amphiphilicities was surveyed by pairing a cationic oxanorbornene with eleven different non-polar monomers and varying the comonomer feed ratios. Their properties were tested using antimicrobial assays and copolymers possessing intermediate hydrophobicities were the most active. Polymer-induced leakage of dye-filled liposomes and microscopy of polymer-treated bacteria support a membrane-based mode of action. From these results there appears to be profound differences in how a polymer made from FA monomers interacts with the phospholipid bilayer compared with copolymers from segregated monomers. We conclude that a well-defined spatial relationship of the whole polymer is crucial to obtain synthetic mimics of antimicrobial peptides (SMAMPs): charged and non-polar moieties need to be balanced locally, for example, at the monomer level, and not just globally. We advocate the use of FA monomers for better control of biological properties. It is expected that this principle will be usefully applied to other backbones such as the polyacrylates, polystyrenes, and non-natural polyamides. PMID:19021176

  5. Rapidly recovering hydrogel scaffolds from self-assembling diblock copolypeptide amphiphiles

    Science.gov (United States)

    Nowak, Andrew P.; Breedveld, Victor; Pakstis, Lisa; Ozbas, Bulent; Pine, David J.; Pochan, Darrin; Deming, Timothy J.

    2002-05-01

    Protein-based hydrogels are used for many applications, ranging from food and cosmetic thickeners to support matrices for drug delivery and tissue replacement. These materials are usually prepared using proteins extracted from natural sources, which can give rise to inconsistent properties unsuitable for medical applications. Recent developments have utilized recombinant DNA methods to prepare artificial protein hydrogels with specific association mechanisms and responsiveness to various stimuli. Here we synthesize diblock copolypeptide amphiphiles containing charged and hydrophobic segments. Dilute solutions of these copolypeptides would be expected to form micelles; instead, they form hydrogels that retain their mechanical strength up to temperatures of about 90°C and recover rapidly after stress. The use of synthetic materials permits adjustment of copolymer chain length and composition, which we varied to study their effect on hydrogel formation and properties. We find that gelation depends not only on the amphiphilic nature of the polypeptides, but also on chain conformations-α-helix, β-strand or random coil. Indeed, shape-specific supramolecular assembly is integral to the gelation process, and provides a new class of peptide-based hydrogels with potential for applications in biotechnology.

  6. Facially amphiphilic thiol capped gold and silver nanoparticles

    OpenAIRE

    Bhat, Shreedhar; Maitra, Uday

    2008-01-01

    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.

  7. Facially amphiphilic thiol capped gold and silver nanoparticles

    Indian Academy of Sciences (India)

    Shreedhar Bhata; Uday Maitra

    2008-11-01

    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.

  8. Amphiphilic vinyl polymers effectively prolong liposome circulation time in vivo.

    Science.gov (United States)

    Torchilin, V P; Shtilman, M I; Trubetskoy, V S; Whiteman, K; Milstein, A M

    1994-10-12

    Newly synthesized amphiphilic polyacrylamide and poly(vinyl pyrrolidone), single terminus-modified with long-chain fatty acyl groups, are able to incorporate into the liposomal membrane, and similar to poly(ethylene glycol) prolong liposome circulation in vivo and decrease liposome accumulation in the liver. Protective efficacy of modified polymers increases with the increase in the length of acyl moiety and decreases for higher molecular weight polymers. The data on amphiphilic polymer-modified liposome biodistribution are presented.

  9. 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.

  10. Effect of IKVAV Peptide Nanofiber on Proliferation,Adhesion and Differentiation into Neurocytes of Bone Marrow Stromal Cells

    Institute of Scientific and Technical Information of China (English)

    吴斌; 郑启新; 吴永超; 郭晓东; 邹枕玮

    2010-01-01

    This study examined the effect of IKVAV peptide nanofiber on proliferation,adhesion and differentiation into neurocytes of bone marrow stromal cells(BMSCs).IKVAV Peptide-amphiphile was synthesized and purified.Then,hydrogen chloride was added to the diluted aqueous solutions of PA to induce spontaneous formation of nanofiber in vitro.The resultant samples was observed under transmission electron microscope.BMSCs were cultured with IKVAV peptide nanofiber.The effect of IKVAV nanofiber on the proliferation,ad...

  11. Wetting in mixtures of water, nonionic amphiphiles, and nonpolar solvents

    Science.gov (United States)

    Kahlweit, M.; Busse, G.

    1989-07-01

    As is well known, medium- and long-chain alkanes do not spread across H2O-air interfaces, but shape a lens. In this paper it is shown that the same holds for the upper amphiphile-rich phase in binary H2O-amphiphile mixtures with medium- and long-chain nonionic amphiphiles that show a (closed) miscibility gap with water. This finding is somewhat unexpected because surfactants form monolayers at H2O-air interfaces which should facilitate the spreading of the amphiphile-rich phase. This wetting behavior corresponds to that in ternary H2O-oil-nonionic amphiphile mixtures with a three-phase body, in which the middle amphiphile-rich phase does not spread across the H2O-oil interface. The results may stimulate further studies on critical-point wetting [for a recent review see, e.g., S. Dietrich, in Phase Transitions and Critical Phenomena, edited by C. Domb and J. L. Lebowitz (Academic, London, 1988), Vol. 12, p. 1.], and may also help clarifying the properties of microemulsions [for a recent review see, e.g., M. Kahlweit, R. Strey, P. Firman, D. Haase, J. Jen, and R. Schomäcker, Langmuir 4, 499 (1988)].

  12. Revealing Amphiphilic Nanodornains of Anti-Biofouling Polymer Coatings

    Energy Technology Data Exchange (ETDEWEB)

    Amadei, CA; Yang, R; Chiesa, M; Gleason, KK; Santos, S

    2014-04-09

    Undesired bacterial adhesion and biofilm formation on wetted surfaces leads to significant economic and environmental costs in various industries. Amphiphilic coatings with molecular hydrophilic and hydrophobic patches can mitigate such biofouling effectively in an environmentally friendly manner. The coatings are synthesized by copolymerizing (Hydroxyethyl)methacrylate and perfluorodecylacrylate via initiated chemical vapor deposition (iCVD). In previous studies, the size of the patches was estimated to be similar to 1.4-1.75 nm by fitting protein adsorption data to a theoretical model. However, no direct observations of the molecular heterogeneity exist and therefore the origin of the fouling resistance of amphiphilic coatings remains unclear. Here, the amphiphilic nature is investigated by amplitude modulation atomic force microscopy (AM-AFM). High-resolution images obtained by penetrating and oscillating the AFM tip under the naturally present water layer with sub-nanometer amplitudes reveal, for the first time, the existence of amphiphilic nanodomains (1-2 nm(2)). Compositional heterogeneity at the nanoscale is further corroborated by a statistical analysis on the data obtained with dynamic AM-AFM force spectroscopy. Variations in the long range attractive forces, responsible for water affinity, are also identified. These nanoscopic results on the polymers wettability are also confirmed by contact angle measurements (i.e., static and dynamic). The unprecedented ability to visualize the amphiphilic nanodomains as well as sub-nanometer crystalline structures provides strong evidence for the existence of previously postulated nanostructures, and sheds light on the underlying antifouling mechanism of amphiphilic chemistry.

  13. Conversion of green fluorescent protein into a toxic, aggregation-prone protein by C-terminal addition of a short peptide.

    Science.gov (United States)

    Link, Christopher D; Fonte, Virginia; Hiester, Brian; Yerg, John; Ferguson, Jmil; Csontos, Susan; Silverman, Michael A; Stein, Gretchen H

    2006-01-20

    A non-natural 16-residue "degron" peptide has been reported to convey proteasome-dependent degradation when fused to proteins expressed in yeast (Gilon, T., Chomsky, O., and Kulka, R. (2000) Mol. Cell. Biol. 20, 7214-7219) or when fused to green fluorescent protein (GFP) and expressed in mammalian cells (Bence, N. F., Sampat, R. M., and Kopito, R. R. (2001) Science 292, 1552-1555). We find that expression of the GFP::degron in Caenorhabditis elegans muscle or neurons results in the formation of stable perinuclear deposits. Similar perinuclear deposition of GFP::degron was also observed upon transfection of primary rat hippocampal neurons or mouse Neuro2A cells. The generality of this observation was supported by transfection of HEK 293 cells with both GFP::degron and DsRed(monomer)::degron constructs. GFP::degron expressed in C. elegans is less soluble than unmodified GFP and induces the small chaperone protein HSP-16, which co-localizes and co-immunoprecipitates with GFP::degron deposits. Induction of GFP::degron in C. elegans muscle leads to rapid paralysis, demonstrating the in vivo toxicity of this aggregating variant. This paralysis is suppressed by co-expression of HSP-16, which dramatically alters the subcellular distribution of GFP::degron. Our results suggest that in C. elegans, and perhaps in mammalian cells, the degron peptide is not a specific proteasome-targeting signal but acts instead by altering GFP secondary or tertiary structure, resulting in an aggregation-prone form recognized by the chaperone system. This altered form of GFP can form toxic aggregates if its expression level exceeds the capacity of chaperone-based degradation pathways. GFP::degron may serve as an instructive "generic" aggregating control protein for studies of disease-associated aggregating proteins, such as huntingtin, alpha-synuclein, and the beta-amyloid peptide. PMID:16239215

  14. Recent advances in amphiphilic polymers for simultaneous delivery of hydrophobic and hydrophilic drugs.

    Science.gov (United States)

    Martin, Chloe; Aibani, Noorjahan; Callan, John F; Callan, Bridgeen

    2016-01-01

    Nanomedicine has evolved with the use of biological compounds such as proteins, peptides and DNA. These hydrophilic and often highly charged compounds require a delivery system to allow effective transport and release at the site of action. These new biological therapeutics have not replaced the more traditional smaller molecule, but instead are working synergistically to the benefit of the end user. To that end, drug delivery systems are now required to encapsulate both larger hydrophilic compounds as well as the smaller and generally more hydrophobic compound. This review highlights the emerging role in drug delivery of amphiphilic polymers that by their very nature can associate with compounds of differing physicochemical properties, in particular the role of micelles, polymersomes and nanocapsules.

  15. Design of a shear-thinning recoverable peptide hydrogel from native sequences and application for influenza H1N1 vaccine adjuvant

    Science.gov (United States)

    Peptide hydrogels are considered injectable materials for drug delivery and tissue engineering applications. Most published hydrogel-forming sequences contain either alternating-charged and noncharged residues or amphiphilic blocks. Here, we report a self-assembling peptide, h9e (FLIVIGSIIGPGGDGPGGD...

  16. Inhibition of VEGF mediated corneal neovascularization by anti-angiogenic peptide nanofibers.

    Science.gov (United States)

    Senturk, Berna; Cubuk, M Ozgur; Ozmen, M Cuneyt; Aydin, Bahri; Guler, Mustafa O; Tekinay, Ayse B

    2016-11-01

    Atypical angiogenesis is one of the major symptoms of severe eye diseases, including corneal neovascularization, and the complex nature of abnormal vascularization requires targeted methods with high biocompatibility. The targeting of VEGF is the most common approach for preventing angiogenesis, and the LPPR peptide sequence is known to strongly inhibit VEGF activity by binding to the VEGF receptor neuropilin-1. Here, the LPPR epitope is presented on a peptide amphiphile nanofiber system to benefit from multivalency and increase the anti-angiogenic function of the epitope. Peptide amphiphile nanofibers are especially useful for ocular delivery applications due to their ability to remain on the site of interest for extended periods of time, facilitating the long-term presentation of bioactive sequences. Consequently, the LPPR sequence was integrated into a self-assembled peptide amphiphile network to increase its efficiency in the prevention of neovascularization. Anti-angiogenic effects of the peptide nanofibers were investigated by using both in vitro and in vivo models. LPPR-PA nanofibers inhibited endothelial cell proliferation, tube formation, and migration to a greater extent than the soluble LPPR peptide in vitro. In addition, the LPPR-PA nanofiber system led to the prevention of vascular maturation and the regression of angiogenesis in a suture-induced corneal angiogenesis model. These results show that the anti-angiogenic activity exhibited by LPPR peptide nanofibers may be utilized as a promising approach for the treatment of corneal angiogenesis. PMID:27616429

  17. 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.

  18. Amphiphilic block copolymers as flexible membrane materials generating structural and functional mimics of green bacterial antenna complexes.

    Science.gov (United States)

    Collins, A M; Timlin, J A; Anthony, S M; Montaño, G A

    2016-08-11

    We describe the ability of a short-chain amphiphilic block copolymer to self-assemble to form an artificial supramolecular light-harvesting system. Specifically, we demonstrate that the 2.5 kDa, poly(ethylene oxide)-block-poly(butadiene) (PEO-b-PBD), exhibits sufficient morphological flexibility as a membrane material and enables generation of mimics of three-dimensional chlorosomes as well as supported membrane bilayers containing energy acceptors. This overall architecture replicates green bacterial light-harvesting function whereby these assemblies exhibit long-range order and three-dimensional morphology similar to native chlorosomes and are capable of energy transfer internally and to external acceptors, located in a supporting biomimetic polymer membrane. Unlike native green bacterial systems that use multiple lipids as a matrix to generate the appropriate environment for chlorosome assembly and function, the described system matrix is comprised entirely of a single polymer amphiphile. This work demonstrates the potential of short-chain amphiphilic block copolymers in generating self-assembled, bio-mimetic membrane architectures, and in doing so, generates scalable, spatial-energetic landscapes for photonic applications. Finally, the results presented provide evidence of minimal requirements to induce chlorosome-like organization and function. PMID:27481550

  19. Liquid Crystalline Nanodispersions Functionalized with Cell-Penetrating Peptides for Topical Delivery of Short-Interfering RNAs: A Proposal for Silencing a Pro-Inflammatory Cytokine in Cutaneous Diseases.

    Science.gov (United States)

    Petrilli, R; Eloy, J O; Praça, F S G; Del Ciampo, J O; Fantini, M A C; Fonseca, M J V; Bentley, M V L B

    2016-05-01

    Short-interfering RNAs (siRNAs) are a potential strategy for the treatment of cutaneous diseases. In this context, liquid crystalline nanoparticles functionalized with specific proteins and peptide-transduction domains (PTDs), which act as penetration enhancers, are a promising carrier for siRNA delivery through the skin. Herein, hexagonal phase liquid crystal nanoparticles based on monoolein (MO) and/or oleic acid (OA) containing (or lacking) the cationic polymer polyethylenimine (PEI) and the cationic lipid oleylamine (OAM) were functionalized with the membrane transduction peptides transcriptional activator (TAT) or penetratin (PNT). These nanoparticles were complexed with siRNA and characterized by particle size, polydispersity, zeta potential, complexation efficiency and siRNA release. The formulations containing cationic agents presented positive zeta potentials, sizes on the nanometer scale, and complexed siRNAs at concentrations of 10 μM; these agents were successfully released in a heparin competition assay. Cell culture studies demonstrated that nanoparticles composed of MO:OA:PEI functionalized with TAT were the most efficient at transfecting L929 cells, and the uptake efficiency was enhanced by TAT peptide functionalization. Thereafter, the selected formulations were evaluated for in vivo skin irritation, penetration and in vivo efficacy using a chemically induced inflammatory animal model. These nanoparticles did not irritate the skin and provided higher siRNA penetration and delivery into the skin than control formulations. Additionally, efficacy studies in the animal model showed that the association of TAT with the nanodispersion provided higher suppression of tumor necrosis factor (TNF)-α. Thus, the development of liquid crystalline nanodispersions containing TAT may lead to improved topical siRNA delivery for the treatment of inflammatory skin diseases. PMID:27305826

  20. 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 S

  1. Repurposing Cationic Amphiphilic Antihistamines for Cancer Treatment

    DEFF Research Database (Denmark)

    Ellegaard, Anne-Marie; Dehlendorff, Christian; Vind, Anna C.;

    2016-01-01

    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 the...... 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...... 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...

  2. 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.

  3. 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. PMID:27333030

  4. Antimicrobial peptides: natural templates for synthetic membrane-active compounds.

    Science.gov (United States)

    Giuliani, A; Pirri, G; Bozzi, A; Di Giulio, A; Aschi, M; Rinaldi, A C

    2008-08-01

    The innate immunity of multicellular organisms relies in large part on the action of antimicrobial peptides (AMPs) to resist microbial invasion. Crafted by evolution into an extremely diversified array of sequences and folds, AMPs do share a common amphiphilic 3-D arrangement. This feature is directly linked with a common mechanism of action that predominantly (although not exclusively) develops upon interaction of peptides with cell membranes of target cells. This minireview reports on current understanding of the modes of interaction of AMPs with biological and model membranes, especially focusing on recent insights into the folding and oligomerization requirements of peptides to bind and insert into lipid membranes and exert their antibiotic effects. Given the potential of AMPs to be developed into a new class of anti-infective agents, emphasis is placed on how the information on peptide-membrane interactions could direct the design and selection of improved biomimetic synthetic peptides with antibiotic properties.

  5. Synthesis of Bioinspired Carbohydrate Amphiphiles that Promote and Inhibit Biofilms.

    Science.gov (United States)

    Dane, Eric L; Ballok, Alicia E; O'Toole, George A; Grinstaff, Mark W

    2014-02-01

    The synthesis and characterization of a new class of bioinspired carbohydrate amphiphiles that modulate Pseudomonas aeruginosa biofilm formation are reported. The carbohydrate head is an enantiopure poly-amido-saccharide (PAS) prepared by a controlled anionic polymerization of β-lactam monomers derived from either glucose or galactose. The supramolecular assemblies formed by PAS amphiphiles are investigated in solution using fluorescence assays and dynamic light scattering. Dried samples are investigated using X-ray, infrared spectroscopy, and transmission electron microscopy. Additionally, the amphiphiles are evaluated for their ability to modulate biofilm formation by the Gram-negative bacterium Pseudomonas aeruginosa. Remarkably, from a library of eight amphiphiles, we identify a structure that promotes biofilm formation and two structures that inhibit biofilm formation. Using biological assays and electron microscopy, we relate the chemical structure of the amphiphiles to the observed activity. Materials that modulate the formation of biofilms by bacteria are important both as research tools for microbiologists to study the process of biofilm formation and for their potential to provide new drug candidates for treating biofilm-associated infections.

  6. 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.

  7. A New Class of Amphiphiles Bearing Rigid Hydrophobic Groups for Solubilization and Stabilization of Membrane Proteins

    DEFF Research Database (Denmark)

    Chae, Pil Seok; Rasmussen, Søren G F; Rana, Rohini R;

    2012-01-01

    Non-traditional amphiphiles: Conferring aqueous solubility on membrane proteins generally requires the use of a detergent or other amphiphilic agent. A new class of amphiphiles was synthesized, based on steroidal lipophilic groups, and evaluated with several membrane proteins. The results show th...

  8. Membrane-bound structure and alignment of the antimicrobial {beta}-sheet peptide gramicidin S derived from angular and distance constraints by solid state 19F-NMR

    Energy Technology Data Exchange (ETDEWEB)

    Salgado, Jesus; Grage, Stephan L. [University of Jena, Department of Molecular Biology (Germany); Kondejewski, Leslie H. [University of Alberta, Protein Engineering Network of Centres of Excellence (Canada); Hodges, Robert S.; McElhaney, Ronald N. [University of Alberta, Department of Biochemistry (Canada); Ulrich, Anne S. [University of Jena, Department of Molecular Biology (Germany)

    2001-11-15

    The antimicrobial properties of the cyclic {beta}-sheet peptide gramicidin S are attributed to its destabilizing effect on lipid membranes. Here we present the membrane-bound structure and alignment of a derivative of this peptide, based on angular and distance constraints. Solid-state {sup 19}F-NMR was used to study a {sup 19}F-labelled gramicidin S analogue in dimyristoylphosphatidylcholine bilayers at a lipid:peptide ratio of 80:1 and above. Two equivalent leucine side chains were replaced by the non-natural amino acid 4F-phenylglycine, which serves as a highly sensitive reporter on the structure and dynamics of the peptide backbone. Using a modified CPMG multipulse sequence, the distance between the two {sup 19}F-labels was measured from their homonuclear dipolar coupling as 6 A, in good agreement with the known backbone structure of natural gramicidin S in solution. By analyzing the anisotropic chemical shift of the {sup 19}F-labels in macroscopically oriented membrane samples, we determined the alignment of the peptide in the bilayer and described its temperature-dependent mobility. In the gel phase, the {sup 19}F-labelled gramicidin S is aligned symmetrically with respect to the membrane normal, i.e., with its cyclic {beta}-sheet backbone lying flat in the plane of the bilayer, which is fully consistent with its amphiphilic character. Upon raising the temperature to the liquid crystalline state, a considerable narrowing of the {sup 19}F-NMR chemical shift dispersion is observed, which is attributed the onset of global rotation of the peptide and further wobbling motions. This study demonstrates the potential of the {sup 19}F nucleus to describe suitably labelled polypeptides in membranes, requiring only little material and short NMR acquisition times.

  9. Redox-controllable amphiphilic [2]rotaxanes.

    Science.gov (United States)

    Tseng, Hsian-Rong; Vignon, Scott A; Celestre, Paul C; Perkins, Julie; Jeppesen, Jan O; Di Fabio, Alberto; Ballardini, Roberto; Gandolfi, M Teresa; Venturi, Margherita; Balzani, Vincenzo; Stoddart, J Fraser

    2004-01-01

    With the fabrication of molecular electronic devices (MEDs) and the construction of nanoelectromechanical systems (NEMSs) as incentives, two constitutionally isomeric, redox-controllable [2]rotaxanes have been synthesized and characterized in solution. Therein, they both behave as near-perfect molecular switches, that is, to all intents and purposes, these two rotaxanes can be switched precisely by applying appropriate redox stimuli between two distinct chemomechanical states. Their dumbbell-shaped components are composed of polyether chains interrupted along their lengths by i) two pi-electron rich recognition sites-a tetrathiafulvalene (TTF) unit and a 1,5-dioxynaphthalene (DNP) moiety-with ii) a rigid terphenylene spacer placed between the two recognition sites, and then terminated by iii) a hydrophobic tetraarylmethane stopper at one end and a hydrophilic dendritic stopper at the other end of the dumbbells, thus conferring amphiphilicity upon these molecules. A template-directed protocol produces a means to introduce the tetracationic cyclophane, cyclobis(paraquat-p-phenylene) (CBPQT(4+)), which contains two pi-electron accepting bipyridinium units, mechanically interlocked around the dumbbell-shaped components. Both the TTF unit and the DNP moiety are potential stations for CBPQT(4+), since they can establish charge-transfer and hydrogen bonding interactions with the bipyridinium units of the cyclophane, thereby introducing bistability into the [2]rotaxanes. In both constitutional isomers, (1)H NMR and absorption spectroscopies, together with electrochemical investigations, reveal that the CBPQT(4+) ring is predominantly located on the TTF unit, leading to the existence of a single translational isomer (co-conformation) in both cases. In addition, a model [2]rotaxane, incorporating hydrophobic tetraarylmethane stoppers at both ends of its dumbbell-shaped component, has also been synthesized as a point of reference. Molecular synthetic approaches were used to

  10. 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.

  11. Synthesis of silver nanoparticles in melts of amphiphilic polyesters

    International Nuclear Information System (INIS)

    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. (paper)

  12. Short bowel patients treated for two years with glucagon-like peptide 2 (GLP-2): compliance, safety, and effects on quality of life

    DEFF Research Database (Denmark)

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

    2009-01-01

    years of subcutaneous GLP-2 treatment, 400 microgram TID, intermitted by an 8-week washout period. METHODS: Safety and compliance was evaluated during the admissions. The Sickness Impact Profile (SIP), Short Form 36 (SF 36), and Inflammatory Bowel Disease Questionnaire (IBDQ) evaluated quality of life......-ascendo-anastomosis. The investigator excluded a patient due to unreliable feedback. Stoma nipple enlargement was seen in all 9 jejunostomy patients. Reported GLP-2 compliance was excellent (>93%). GLP-2 improved the overall quality of life VAS-score (4.1 +/- 2.8 cm versus 6.0 +/- 2.4 cm, P SIP score (10.3 +/- 8...

  13. 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.

  14. Self-assembled peptide beads used as a template for ordered gold nanoparticle superstructures.

    Science.gov (United States)

    de Bruyn Ouboter, Dirk; Schuster, Thomas B; Sigg, Severin J; Meier, Wolfgang P

    2013-12-01

    Using peptide-based materials to tailor self-assembled, nano-scaled hybrid materials with potentially high biocompatibility/biodegradability is gaining importance in developing a broad range of new applications, in areas such as diagnostics and medicine. Here, we investigated how the self-assembly ability of amphiphilic peptides can be used to create organized inorganic materials, i.e. gold nanoparticles. A bead-forming, purely peptidic amphiphile Ac-[K(Ac)]3-[W-l]3-W-NH2, containing acetylated (Ac) l-lysine (K), l-tryptophan (W) and d-leucine (l), was C-terminally modified with a l-cysteine (C) and linked to gold nanoparticles. Subsequent peptide-driven self-assembly of the peptide-coated gold nanoparticles with increasing water content led to controlled aggregation of the gold-core micelles, forming composite peptide-gold superstructures. The individual gold nanoparticles did not agglomerate but were separated from each other by a peptide film within the composite material, as revealed by electron microscopy studies. Structural investigation on 2D template-stripped gold demonstrated the ability of the peptides to form self-assembled monolayers. Structural elements of β-turns and weak hydrogen bonding of the hydrophobic moiety of the peptide were evident, thereby suggesting that the secondary structure remains intact. PMID:24099645

  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

    2015-02-01

    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

  16. Cationic amphiphilic non-hemolytic polyacrylates with superior antibacterial activity.

    Science.gov (United States)

    Punia, Ashish; He, Edward; Lee, Kevin; Banerjee, Probal; Yang, Nan-Loh

    2014-07-01

    Acrylic copolymers with appropriate compositions of counits having cationic charge with 2-carbon and 6-carbon spacer arms can show superior antibacterial activities with concomitant very low hemolytic effect. These amphiphilic copolymers represent one of the most promising synthetic polymer antibacterial systems reported. PMID:24854366

  17. Langmuir monolayer formation of metal complexes from polymerizable amphiphilic ligands

    NARCIS (Netherlands)

    Werkman, PJ; Schouten, AJ

    1996-01-01

    The monolayer behaviour of 4-(10,12-pentacosadiynoicamidomethyl)-pyridine at the air-water interface was studied by measuring the surface pressure-area isotherms. The amphiphile formed stable monolayers with a clear liquid-expanded (LE) to liquid-condensed phase transition at various temperatures. U

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

    International Nuclear Information System (INIS)

    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 (EC5: 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 (EC5: 19.1 ± 17.3). Nonionic amphiphiles did not affect BWS. The longer-chain perfluorinated carboxylates PFNA and PFDA were more potent than PFOA (EC5: 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

  19. Bio-based amphiphilic materials development and applications

    Science.gov (United States)

    Farm-based raw materials are increasingly used in the development of amphiphilic materials that have potential applications in the production of a variety of consumer and industrial products, including lubricants. Raw materials of interest include: starches, proteins, fats, oils, and sugars. These ...

  20. Amphiphiles containing aromatic groups in the hydrophobic part

    NARCIS (Netherlands)

    Visscher, Inge

    2004-01-01

    Aggregation processes are essential for life on this planet. For example, the membranes of all living cells are bilayered aggregates, consisting of lipid molecules, proteins and steroids. In many biological processes, aggregates play a role. The main driving force for aggregation of amphiphiles is h

  1. Microphase separation of diblock copolymers with amphiphilic segment

    NARCIS (Netherlands)

    Kriksin, Yury A.; Khalatur, Pavel G.; Erukhimovich, Igor Ya.; ten Brinke, Gerrit; Khokhlov, Alexei R.

    2009-01-01

    We present a statistical mechanical approach for predicting the self-assembled morphologies of amphiphilic diblock copolymers in the melt. We introduce two conformationally asymmetric linear copolymer models with a local structural asymmetry, one of a "comb-tail'' type and another that we call "cont

  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. Short communication: Identification of iron-binding peptides from whey protein hydrolysates using iron (III)-immobilized metal ion affinity chromatography and reversed phase-HPLC-tandem mass spectrometry.

    Science.gov (United States)

    Cruz-Huerta, Elvia; Martínez Maqueda, Daniel; de la Hoz, Lucia; da Silva, Vera S Nunes; Pacheco, Maria Teresa Bertoldo; Amigo, Lourdes; Recio, Isidra

    2016-01-01

    Peptides with iron-binding capacity obtained by hydrolysis of whey protein with Alcalase (Novozymes, Araucaria, PR, Brazil), pancreatin, and Flavourzyme (Novozymes) were identified. Hydrolysates were subjected to iron (III)-immobilized metal ion affinity chromatography, and the bound peptides were sequenced by mass spectrometry. Regardless of the enzyme used, the domains f(42-59) and f(125-137) from β-lactoglobulin enclosed most of identified peptides. This trend was less pronounced in the case of peptides derived from α-lactalbumin, with sequences deriving from diverse regions. Iron-bound peptides exhibited common structural characteristics, such as an abundance of Asp, Glu, and Pro, as revealed by mass spectrometry and AA analysis. In conclusion, this characterization of iron-binding peptides helps clarify the relationship between peptide structure and iron-chelating activity and supports the promising role of whey protein hydrolysates as functional ingredients in iron supplementation treatments. PMID:26601589

  4. 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. PMID:25366889

  5. 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.

  6. Structural characterization of amphiphilic siderophores produced by a soda lake isolate, Halomonas sp. SL01, reveals cysteine-, phenylalanine- and proline-containing head groups.

    Science.gov (United States)

    Figueroa, Luis O'mar Serrano; Schwarz, Benjamin; Richards, Abigail M

    2015-11-01

    Soap Lake, located in Washington State, is a naturally occurring saline and alkaline lake. Several organisms inhabiting this lake have been identified as producers of siderophores that are unique in structure. Bacterial isolates, enriched from Soap Lake sediment and water samples, were screened for siderophore production using both the chrome azurol S (CAS) agar plate and liquid methods. Bacterial isolate Halomonas sp. SL01 was found to produce relatively high concentrations of siderophores in liquid medium (up to 40 µM). Siderophores from the isolate were separated from the culture supernatant using solid phase extraction and purified by high-performance liquid chromatography (HPLC). Siderophore structure was determined using LC/MS/MS (liquid chromatography/mass spectrometry/mass spectrometry) and fatty acid methyl ester (FAME) GC. Two distinct new families of amphiphilic siderophores were produced by isolate SL01. All siderophores ranged in size from 989 to 1096 atomic mass units and consisted of a conserved peptidic head group (per family), which coordinates iron, coupled to fatty acid moieties. The fatty acyl moieties were C10-C14 in length and some with hydroxyl substitutions at the third α position. These siderophores resembled amphiphilic aquachelin siderophores produced by Halomonas aquamarina strain DS40M3, a marine bacterium as well as siderophores from isolate Halomonas sp. SL28 that was found to produce amphiphilic siderophores. Bacteria thriving under saline and alkaline conditions are capable of producing unique siderophores resembling those produced by microbes inhabiting marine environments. PMID:26439615

  7. Periodically Grafted Amphiphilic Copolymers: Effects of Steric Crowding and Reversal of Amphiphilicity.

    Science.gov (United States)

    Mandal, Joydeb; Ramakrishnan, S

    2015-06-01

    Two series of periodically clickable polyesters were prepared; one of them carries alkylene segments along its backbone, whereas the other carries poly(ethylene glycol) (PEG) segments. These polyesters were clicked with either MPEG-350 azide or docosyl (C22) azide to yield periodically grafted amphiphilic copolymers (PGACs) carrying either flexible hydrophilic or crystallizable hydrophobic backbone segments. The immiscibility between hydrocarbon and PEG segments causes both of these systems to fold in either a zigzag or hairpin-like conformation; the hairpin-like conformation appears to be preferred when flexible PEG segments are present in the backbone. The folded chains further reorganize in the solid state to develop a lamellar morphology that permits the collocation of the PEG and hydrocarbon (HC) segments within alternate domains; evidence for the self-segregation was gained from DSC, SAXS, and AFM studies. SAXS studies revealed the formation of an extended lamellar structure, whereas AFM images showed uniform layered morphology with layer heights that matched reasonably well with the interlamellar spacing obtained from the SAXS study. Labeling one representative PGAC, carrying crystallizable long alkylene segments in the backbone and pendant PEG-350 side chains, with a small mole fraction of pyrene fluorophore permitted the examination of the conformational transition that occurs upon going from a good to a poor solvent; this single-chain folded conformation, we postulate, is the intermediate that organizes into the lamellar morphology.

  8. Synthesis, characterization and comparative evaluation of phenoxy ring containing long chain gemini imidazolium and pyridinium amphiphiles.

    Science.gov (United States)

    Bhadani, Avinash; Kataria, Hardeep; Singh, Sukhprit

    2011-09-01

    Two series of phenoxy ring containing long chain imidazolium and pyridinium based gemini amphiphiles have been synthesized from renewable cardanol oil having different spacers (i. e. -S-(CH(2))(n)-S-, where n is 2, 3, 4 & 6). Critical micelle concentration (cmc) of these new gemini amphiphiles has been determined by conductivity method. Further, these new cationic amphiphiles have been evaluated for their DNA binding capability by agarose gel electrophoresis, ethidium bromide exclusion experiments and transmission electron microscopy (TEM). The cytotoxicity of these new amphiphiles have been evaluated by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Comparative studies of these phenoxy ring containing long chain gemini imidazolium amphiphiles and their pyridinium analogues depicted low cmc values of the later but greater DNA interaction capability and low cytotoxicity of the former series of amphiphiles. PMID:21676409

  9. Stealth Amphiphiles: Self-Assembly of Polyhedral Boron Clusters.

    Science.gov (United States)

    Ďorďovič, Vladimír; Tošner, Zdeněk; Uchman, Mariusz; Zhigunov, Alexander; Reza, Mehedi; Ruokolainen, Janne; Pramanik, Goutam; Cígler, Petr; Kalíková, Květa; Gradzielski, Michael; Matějíček, Pavel

    2016-07-01

    This is the first experimental evidence that both self-assembly and surface activity are common features of all water-soluble boron cluster compounds. The solution behavior of anionic polyhedral boranes (sodium decaborate, sodium dodecaborate, and sodium mercaptododecaborate), carboranes (potassium 1-carba-dodecaborate), and metallacarboranes {sodium [cobalt bis(1,2-dicarbollide)]} was extensively studied, and it is evident that all the anionic boron clusters form multimolecular aggregates in water. However, the mechanism of aggregation is dependent on size and polarity. The series of studied clusters spans from a small hydrophilic decaborate-resembling hydrotrope to a bulky hydrophobic cobalt bis(dicarbollide) behaving like a classical surfactant. Despite their pristine structure resembling Platonic solids, the nature of anionic boron cluster compounds is inherently amphiphilic-they are stealth amphiphiles. PMID:27287067

  10. Multidimensional hierarchical self-assembly of amphiphilic cylindrical block comicelles

    Science.gov (United States)

    Qiu, Huibin; Hudson, Zachary M.; Winnik, Mitchell A.; Manners, Ian

    2015-03-01

    Self-assembly of molecular and block copolymer amphiphiles represents a well-established route to micelles with a wide variety of shapes and gel-like phases. We demonstrate an analogous process, but on a longer length scale, in which amphiphilic P-H-P and H-P-H cylindrical triblock comicelles with hydrophobic (H) or polar (P) segments that are monodisperse in length are able to self-assemble side by side or end to end in nonsolvents for the central or terminal segments, respectively. This allows the formation of cylindrical supermicelles and one-dimensional (1D) or 3D superstructures that persist in both solution and the solid state. These assemblies possess multiple levels of structural hierarchy in combination with existence on a multimicrometer-length scale, features that are generally only found in natural materials.

  11. Three-dimensional structure in lipid micelles of the pediocin-like antimicrobial peptide curvacin A.

    Science.gov (United States)

    Haugen, Helen Sophie; Fimland, Gunnar; Nissen-Meyer, Jon; Kristiansen, Per Eugen

    2005-12-13

    The 3D structure of the membrane-permeabilizing 41-mer pediocin-like antimicrobial peptide curvacin A produced by lactic acid bacteria has been studied by NMR spectroscopy. In DPC micelles, the cationic and hydrophilic N-terminal half of the peptide forms an S-shaped beta-sheet-like domain stabilized by a disulfide bridge and a few hydrogen bonds. This domain is followed by two alpha-helices: a hydrophilic 6-mer helix between residues 19 and 24 and an amphiphilic/hydrophobic 11-mer helix between residues 29 and 39. There are two hinges in the peptide, one at residues 16-18 between the N-terminal S-shaped beta-sheet-like structure and the central 6-mer helix and one at residues 26-28 between the central helix and the 11-mer C-terminal helix. The latter helix is the only amphiphilic/hydrophobic part of the peptide and is thus presumably the part that penetrates into the hydrophobic phase of target-cell membranes. The hinge between the two helices may introduce the flexibility that allows the helix to dip into membranes. The helix-hinge-helix structure in the C-terminal half of curvacin A clearly distinguishes this peptide from the other pediocin-like peptides whose structures have been analyzed and suggests that curvacin A along with the structural homologues enterocin P and carnobacteriocin BM1 belong to a subgroup of the pediocin-like family of antimicrobial peptides. PMID:16331975

  12. Prebiotic Lipidic Amphiphiles and Condensing Agents on the Early Earth.

    Science.gov (United States)

    Fiore, Michele; Strazewski, Peter

    2016-01-01

    It is still uncertain how the first minimal cellular systems evolved to the complexity required for life to begin, but it is obvious that the role of amphiphilic compounds in the origin of life is one of huge relevance. Over the last four decades a number of studies have demonstrated how amphiphilic molecules can be synthesized under plausibly prebiotic conditions. The majority of these experiments also gave evidence for the ability of so formed amphiphiles to assemble in closed membranes of vesicles that, in principle, could have compartmented first biological processes on early Earth, including the emergence of self-replicating systems. For a competitive selection of the best performing molecular replicators to become operative, some kind of bounded units capable of harboring them are indispensable. Without the competition between dynamic populations of different compartments, life itself could not be distinguished from an otherwise disparate array or network of molecular interactions. In this review, we describe experiments that demonstrate how different prebiotically-available building blocks can become precursors of phospholipids that form vesicles. We discuss the experimental conditions that resemble plausibly those of the early Earth (or elsewhere) and consider the analytical methods that were used to characterize synthetic products. Two brief sections focus on phosphorylating agents, catalysts and coupling agents with particular attention given to their geochemical context. In Section 5, we describe how condensing agents such as cyanamide and urea can promote the abiotic synthesis of phospholipids. We conclude the review by reflecting on future studies of phospholipid compartments, particularly, on evolvable chemical systems that include giant vesicles composed of different lipidic amphiphiles. PMID:27043635

  13. Prebiotic Lipidic Amphiphiles and Condensing Agents on the Early Earth

    Directory of Open Access Journals (Sweden)

    Michele Fiore

    2016-03-01

    Full Text Available It is still uncertain how the first minimal cellular systems evolved to the complexity required for life to begin, but it is obvious that the role of amphiphilic compounds in the origin of life is one of huge relevance. Over the last four decades a number of studies have demonstrated how amphiphilic molecules can be synthesized under plausibly prebiotic conditions. The majority of these experiments also gave evidence for the ability of so formed amphiphiles to assemble in closed membranes of vesicles that, in principle, could have compartmented first biological processes on early Earth, including the emergence of self-replicating systems. For a competitive selection of the best performing molecular replicators to become operative, some kind of bounded units capable of harboring them are indispensable. Without the competition between dynamic populations of different compartments, life itself could not be distinguished from an otherwise disparate array or network of molecular interactions. In this review, we describe experiments that demonstrate how different prebiotically-available building blocks can become precursors of phospholipids that form vesicles. We discuss the experimental conditions that resemble plausibly those of the early Earth (or elsewhere and consider the analytical methods that were used to characterize synthetic products. Two brief sections focus on phosphorylating agents, catalysts and coupling agents with particular attention given to their geochemical context. In Section 5, we describe how condensing agents such as cyanamide and urea can promote the abiotic synthesis of phospholipids. We conclude the review by reflecting on future studies of phospholipid compartments, particularly, on evolvable chemical systems that include giant vesicles composed of different lipidic amphiphiles.

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

    OpenAIRE

    Shrestha, Sanjib K.; Cheng-Wei T Chang; Meissner, Nicole; Oblad, John; Shrestha, Jaya P.; Sorensen, Kevin N.; Michelle M. Grilley; Jon Y Takemoto

    2014-01-01

    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 de...

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

    OpenAIRE

    Shrestha, Sanjib K.; Cheng-Wei Tom Chang; Nicole eMeissner; John eOblad; Shrestha, Jaya P.; Sorensen, Kevin N.; Michelle M. Grilley; Jon Y Takemoto

    2014-01-01

    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 d...

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

    International Nuclear Information System (INIS)

    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

  17. From Vesicles to Protocells: The Roles of Amphiphilic Molecules

    OpenAIRE

    Yuka Sakuma; Masayuki Imai

    2015-01-01

    It is very challenging to construct protocells from molecular assemblies. An important step in this challenge is the achievement of vesicle dynamics that are relevant to cellular functions, such as membrane trafficking and self-reproduction, using amphiphilic molecules. Soft matter physics will play an important role in the development of vesicles that have these functions. Here, we show that simple binary phospholipid vesicles have the potential to reproduce the relevant functions of adhes...

  18. A defect mediated lamellar to isotropic transition of amphiphile bilayers

    OpenAIRE

    Pal, Antara; Pabst, Georg; Raghunathan, V. A.

    2011-01-01

    We report the observation of a novel isotropic phase of amphiphile bilayers in a mixed system consisting of the ionic surfactant, sodium docecylsulphate (SDS), and the organic salt p-toludine hydrochloride (PTHC). This system forms a collapsed lamellar ($L_\\alpha$) phase over a wide range of water content, which transforms into an isotropic phase on heating. This transition is not observed in samples without excess water, where the $L_\\alpha$ phase is stable at higher temperatures. Our observ...

  19. The lamellar-to-isotropic transition in ternary amphiphilic systems

    OpenAIRE

    Schwarz, U. S.; Swamy, K.; Gompper, G.

    1996-01-01

    We study the dependence of the phase behavior of ternary amphiphilic systems on composition and temperature. Our analysis is based on a curvature elastic model of the surfactant film with sufficiently large spontaneous curvature and sufficiently negative saddle-splay modulus that the stable phases are the lamellar phase and a droplet microemulsion. In addition to the curvature energy, we consider the contributions to the free energy of the long-ranged van der Waals interaction and of the undu...

  20. Supramolecular Packing Controls H₂ Photocatalysis in Chromophore Amphiphile Hydrogels.

    Science.gov (United States)

    Weingarten, Adam S; Kazantsev, Roman V; Palmer, Liam C; Fairfield, Daniel J; Koltonow, Andrew R; Stupp, Samuel I

    2015-12-01

    Light harvesting supramolecular assemblies are potentially useful structures as components of solar-to-fuel conversion materials. The development of these functional constructs requires an understanding of optimal packing modes for chromophores. We investigated here assembly in water and the photocatalytic function of perylene monoimide chromophore amphiphiles with different alkyl linker lengths separating their hydrophobic core and the hydrophilic carboxylate headgroup. We found that these chromophore amphiphiles (CAs) self-assemble into charged nanostructures of increasing aspect ratio as the linker length is increased. The addition of salt to screen the charged nanostructures induced the formation of hydrogels and led to internal crystallization within some of the nanostructures. For linker lengths up to seven methylenes, the CAs were found to pack into 2D crystalline unit cells within ribbon-shaped nanostructures, whereas the nine methylene CAs assembled into long nanofibers without crystalline molecular packing. At the same time, the different molecular packing arrangements after charge screening led to different absorbance spectra, despite the identical electronic properties of all PMI amphiphiles. While the crystalline CAs formed electronically coupled H-aggregates, only CAs with intermediate linker lengths showed evidence of high intermolecular orbital overlap. Photocatalytic hydrogen production using a nickel-based catalyst was observed in all hydrogels, with the highest turnovers observed for CA gels having intermediate linker lengths. We conclude that the improved photocatalytic performance of the hydrogels formed by supramolecular assemblies of the intermediate linker CA molecules likely arises from improved exciton splitting efficiencies due to their higher orbital overlap. PMID:26593389

  1. High-Capacity Drug Carriers from Common Polymer Amphiphiles.

    Science.gov (United States)

    Zhou, Zhun; Munyaradzi, Oliver; Xia, Xin; Green, Da'Sean; Bong, Dennis

    2016-09-12

    We report herein a dual-purpose role for polyacidic domains in an aqueous-phase polymer amphiphile assembly. In addition to their typical role as ionized water-solubilizing and self-repulsive motifs, we find that polycarboxylic acid domains uniquely enable high levels of hydrophobic drug encapsulation. By attenuated total reflectance infrared spectroscopy, we find significant differences in the carbonyl stretching region of the nanoparticles formed by polyacidic amphiphiles relative to those in soluble, single-domain poly(acrylic acid), suggesting that stabilization may be derived from limited ionization of the carboxylate groups upon assembly. Acidic-hydrophobic diblock polyacrylates were prepared and coassembled with up to 60 wt % camptothecin (CPT) into nanoparticles, the highest loading reported to date. Controlled release of bioactive CPT from polymer nanoparticles is observed, as well as protection from human serum albumin-induced hydrolysis. Surface protection with PEG limits uptake of the CPT-loaded nanoparticles by MCF-7 breast cancer cells, as expected. Acidic-hydrophobic polymer amphiphiles thus have the hallmarks of a useful and general drug delivery platform and are readily accessible from living radical polymerization of cheap, commercially available monomers. We highlight here the potential utility of this common polymer design in high-capacity, controlled-release polymer nanoparticle systems. PMID:27476544

  2. Cationic amphiphiles with fatty acyl chain asymmetry of coconut oil deliver genes selectively to mouse lung.

    Science.gov (United States)

    Chandrashekhar, Voshavar; Srujan, Marepally; Prabhakar, Rairala; Reddy, Rakesh C; Sreedhar, Bojja; Rentam, Kiran K R; Kanjilal, Sanjit; Chaudhuri, Arabinda

    2011-03-16

    Recent structure-activity studies have revealed a dramatic influence of hydrophobic chain asymmetry in enhancing gene delivery efficacies of synthetic cationic amphiphiles (Nantz, M. H. et al. Mol. Pharmaceutics2010, 7, 786-794; Koynova, R. et al. Mol. Pharmaceutics2009, 6, 951-958). The present findings demonstrate for the first time that such a transfection enhancing influence of asymmetric hydrocarbon chains observed in pure synthetic cationic amphiphiles also works for cationic amphiphiles designed with natural, asymmetric fatty acyl chains of a food-grade oil. Herein, we demonstrate that cationic amphiphiles designed with the natural fatty acyl chain asymmetry of food-grade coconut oil are less cytotoxic and deliver genes selectively to mouse lung. Despite lauroyl chains being the major fatty acyl chains of coconut oil, both the in vitro and In vivo gene transfer efficiencies of such cationic amphiphiles were found to be remarkably superior (>4-fold) to those of their pure dilauroyl analogue. Mechanistic studies involving the technique of fluorescence resonance energy transfer (FRET) revealed higher biomembrane fusibility of the cationic liposomes of the coconut amphiphiles than that of the symmetric dilauroyl analogue. AFM study revealed pronounced fusogenic nonlamellar structures of the liposomes of coconut amphiphiles. Findings in the FRET and cellular uptake study, taken together, support the notion that the higher cellular uptake resulting from the more fusogenic nature of the liposomes of coconut amphiphiles 1 are likely to play a dominant role in making the coconut amphiphiles transfection competent.

  3. 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.

  4. Shaping quaternary assemblies of water-soluble non-peptide helical foldamers by sequence manipulation

    Science.gov (United States)

    Collie, Gavin W.; Pulka-Ziach, Karolina; Lombardo, Caterina M.; Fremaux, Juliette; Rosu, Frédéric; Decossas, Marion; Mauran, Laura; Lambert, Olivier; Gabelica, Valérie; Mackereth, Cameron D.; Guichard, Gilles

    2015-11-01

    The design and construction of biomimetic self-assembling systems is a challenging yet potentially highly rewarding endeavour that contributes to the development of new biomaterials, catalysts, drug-delivery systems and tools for the manipulation of biological processes. Significant progress has been achieved by engineering self-assembling DNA-, protein- and peptide-based building units. However, the design of entirely new, completely non-natural folded architectures that resemble biopolymers (‘foldamers’) and have the ability to self-assemble into atomically precise nanostructures in aqueous conditions has proved exceptionally challenging. Here we report the modular design, formation and structural elucidation at the atomic level of a series of diverse quaternary arrangements formed by the self-assembly of short amphiphilic α-helicomimetic foldamers that bear proteinaceous side chains. We show that the final quaternary assembly can be controlled at the sequence level, which permits the programmed formation of either discrete helical bundles that contain isolated cavities or pH-responsive water-filled channels with controllable pore diameters.

  5. Fragment-based solid-phase assembly of oligonucleotide conjugates with peptide and polyethylene glycol ligands.

    Science.gov (United States)

    Dirin, Mehrdad; Urban, Ernst; Noe, Christian R; Winkler, Johannes

    2016-10-01

    Ligand conjugation to oligonucleotides is an attractive strategy for enhancing the therapeutic potential of antisense and siRNA agents by inferring properties such as improved cellular uptake or better pharmacokinetic properties. Disulfide linkages enable dissociation of ligands and oligonucleotides in reducing environments found in endosomal compartments after cellular uptake. Solution-phase fragment coupling procedures for producing oligonucleotide conjugates are often tedious, produce moderate yields and reaction byproducts are frequently difficult to remove. We have developed an improved method for solid-phase coupling of ligands to oligonucleotides via disulfides directly after solid-phase synthesis. A 2'-thiol introduced using a modified nucleotide building block was orthogonally deprotected on the controlled pore glass solid support with N-butylphosphine. Oligolysine peptides and a short monodisperse ethylene glycol chain were successfully coupled to the deprotected thiol. Cleavage from the resin and full removal of oligonucleotide protection groups were achieved using methanolic ammonia. After standard desalting, and without further purification, homogenous conjugates were obtained as demonstrated by HPLC, gel electrophoresis, and mass spectrometry. The attachment of both amphiphilic and cationic ligands proves the versatility of the conjugation procedure. An antisense oligonucleotide conjugate with hexalysine showed pronounced gene silencing in a cell culture tumor model in the absence of a transfection reagent and the corresponding ethylene glycol conjugate resulted in down regulation of the target gene to nearly 50% after naked application. PMID:27236069

  6. Synthesis and characterization of an elastin-mimetic amphiphilic block copolymer protein

    Science.gov (United States)

    Lee, Terrence Anita-Talley

    2000-10-01

    The overall goal in material science is to be able to control the molecular architecture of a material and thus its end properties. There is no method that offers greater control than the biological synthesis of proteins. From the DNA sequence to the final synthesized protein, the entire process is finitely controlled. This present work describes methods developed and used to synthesize protein polymers by manipulating this process. From the initial DNA sequence chosen, the end properties that the protein polymer will have are dictated. An amphiphilic diblock copolymer was designed based on environmentally responsive elastin-mimetic peptide sequences [(Val/Ile)-Pro-Gly-Xaa-Gly] (Xaa = Ala or Glu for the hydrophilic block, Val or Phe for the hydrophobic block) and synthesized using a genetic engineering approach. Differential scanning calorimetry measurements in aqueous solution revealed that reversible hydrophobic folding and assembly of the copolymer occurs above the inverse temperature transition, Tt, of the hydrophobic block. This process results in the formation of 50 nm protein-based micellar aggregates, which were characterized by electron microscopy and temperature-dependent dynamic light scattering techniques. The distribution of micellar aggregates can be altered reproducibly through variation of environmental conditions including pH and temperature. The uniform and defined macromolecular architecture of this protein copolymer permits greater control over the physical properties of the micelles, which therefore may facilitate applications in controlled release of small molecules.

  7. Assembly and Structure of alpha-helical Peptide Films on Hydrophobic Fluorocarbon Surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Weidner, T.; Samual, N; McCrea, K; Gamble, L; Ward, R; Castner, D

    2010-01-01

    The structure, orientation, and formation of amphiphilic {alpha}-helix model peptide films on fluorocarbon surfaces has been monitored with sum frequency generation (SFG) vibrational spectroscopy, near-edge x-ray absorption fine structure (NEXAFS) spectroscopy, and x-ray photoelectron spectroscopy (XPS). The {alpha}-helix peptide is a 14-mer of hydrophilic lysine and hydrophobic leucine residues with a hydrophobic periodicity of 3.5. This periodicity yields a rigid amphiphilic peptide with leucine and lysine side chains located on opposite sides. XPS composition analysis confirms the formation of a peptide film that covers about 75% of the surface. NEXAFS data are consistent with chemically intact adsorption of the peptides. A weak linear dichroism of the amide {pi}* is likely due to the broad distribution of amide bond orientations inherent to the {alpha}-helical secondary structure. SFG spectra exhibit strong peaks near 2865 and 2935 cm{sup -1} related to aligned leucine side chains interacting with the hydrophobic surface. Water modes near 3200 and 3400 cm{sup -1} indicate ordering of water molecules in the adsorbed-peptide fluorocarbon surface interfacial region. Amide I peaks observed near 1655 cm{sup -1} confirm that the secondary structure is preserved in the adsorbed peptide. A kinetic study of the film formation process using XPS and SFG showed rapid adsorption of the peptides followed by a longer assembly process. Peptide SFG spectra taken at the air-buffer interface showed features related to well-ordered peptide films. Moving samples through the buffer surface led to the transfer of ordered peptide films onto the substrates.

  8. 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...

  9. Dehydration-induced redistribution of amphiphilic molecules between cytoplasm and lipids is associated with desiccation tolerance in seeds

    NARCIS (Netherlands)

    Buitink, J.; Leprince, O.; Hoekstra, F.A.

    2000-01-01

    This study establishes a relationship between desiccation tolerance and the transfer of amphiphilic molecules from the cytoplasm into lipids during drying, using electron paramagnetic resonance spectroscopy of amphiphilic spin probes introduced into imbibed radicles of pea (Pisum sativum) and cucumb

  10. REDV Peptide Conjugated Nanoparticles/pZNF580 Complexes for Actively Targeting Human Vascular Endothelial Cells.

    Science.gov (United States)

    Shi, Changcan; Li, Qian; Zhang, Wencheng; Feng, Yakai; Ren, Xiangkui

    2015-09-16

    Herein, we demonstrate that the REDV peptide modified nanoparticles (NPs) can serve as a kind of active targeting gene carrier to condensate pZNF580 for specific promotion of the proliferation of endothelial cells (ECs). First, we synthesized a series of biodegradable amphiphilic copolymers by ring-opening polymerization reaction and graft modification with REDV peptide. Second, we prepared active targeting NPs via self-assembly of the amphiphilic copolymers using nanoprecipitation technology. After condensation with negatively charged pZNF580, the REDV peptide modified NPs/pZNF580 complexes were formed finally. Due to the binding affinity toward ECs of the specific peptide, these REDV peptide modified NPs/pZNF580 complexes could be recognized and adhered specifically by ECs in the coculture system of ECs and human artery smooth muscle cells (SMCs) in vitro. After expression of ZNF580, as the key protein to promote the proliferation of ECs, the relative ZNF580 protein level increased from 15.7% to 34.8%. The specificity in actively targeting ECs of the REDV peptide conjugated NPs/pZNF580 complexes was still retained in the coculture system. These findings in the present study could facilitate the development of actively targeting gene carriers for the endothelialization of artificial blood vessels. PMID:26373583

  11. Stimuli-Responsive Codelivery of Oligonucleotides and Drugs by Self-Assembled Peptide Nanoparticles.

    Science.gov (United States)

    Sigg, Severin J; Postupalenko, Viktoriia; Duskey, Jason T; Palivan, Cornelia G; Meier, Wolfgang

    2016-03-14

    Ever more emerging combined treatments exploiting synergistic effects of drug combinations demand smart, responsive codelivery carriers to reveal their full potential. In this study, a multifunctional stimuli-responsive amphiphilic peptide was designed and synthesized to self-assemble into nanoparticles capable of co-bearing and -releasing hydrophobic drugs and antisense oligonucleotides for combined therapies. The rational design was based on a hydrophobic l-tryptophan-d-leucine repeating unit derived from a truncated sequence of gramicidin A (gT), to entrap hydrophobic cargo, which is combined with a hydrophilic moiety of histidines to provide electrostatic affinity to nucleotides. Stimuli-responsiveness was implemented by linking the hydrophobic and hydrophilic sequence through an artificial amino acid bearing a disulfide functional group (H3SSgT). Stimuli-responsive peptides self-assembled in spherical nanoparticles in sizes (100-200 nm) generally considered as preferable for drug delivery applications. Responsive peptide nanoparticles revealed notable nucleotide condensing abilities while maintaining the ability to load hydrophobic cargo. The disulfide cleavage site introduced in the peptide sequence induced responsiveness to physiological concentrations of reducing agent, serving to release the incorporated molecules. Furthermore, the peptide nanoparticles, singly loaded or coloaded with boron-dipyrromethene (BODIPY) and/or antisense oligonucleotides, were efficiently taken up by cells. Such amphiphilic peptides that led to noncytotoxic, reduction-responsive nanoparticles capable of codelivering hydrophobic and nucleic acid payloads simultaneously provide potential toward combined treatment strategies to exploit synergistic effects. PMID:26871486

  12. 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

    The self-assembly of cationic and anionic amphiphile mixtures into vesicles in aqueous media was studied using two different systems: i) decanoic acid and trimethyldecylammonium bromide ii) hexadecanedioic acid (a simple bola-amphiphile) and trimethyldecylammonium bromide. The resulting vesicles ...

  13. Phosphate bioisostere containing amphiphiles: a novel class of squaramide-based lipids.

    Science.gov (United States)

    Saha, Abhishek; Panda, Subhankar; Paul, Saurav; Manna, Debasis

    2016-07-19

    We describe a novel class of amphiphiles with squaramide moiety as a phosphate bioisostere. Most synthesized squaramide-based amphiphiles have the favorable physicochemical properties of lipids, such as: formation of stable liposomes or giant unilamellar vesicles in aqueous solution, high phase-transition temperature, low vesicle leakage and phospholipase resistance properties. PMID:27377058

  14. Insights into the coassembly of hydrogelators and surfactants based on aromatic peptide amphiphiles.

    Science.gov (United States)

    Fleming, Scott; Debnath, Sisir; Frederix, Pim W J M; Hunt, Neil T; Ulijn, Rein V

    2014-04-14

    The coassembly of small molecules is a useful means of increasing the complexity and functionality of their resultant supramolecular constructs in a modular fashion. In this study, we explore the assembly and coassembly of serine surfactants and tyrosine-leucine hydrogelators, capped at the N-termini with either fluorenyl-9-methoxycarbonyl (Fmoc) or pyrene. These systems all exhibit self-assembly behavior, which is influenced by aromatic stacking interactions, while the hydrogelators also exhibit β-sheet-type arrangements, which reinforce their supramolecular structures. We provide evidence for three distinct supramolecular coassembly models; cooperative, disruptive, and orthogonal. The coassembly mode adopted depends on whether the individual constituents (I) are sufficiently different, such that effective segregation and orthogonal assembly occurs; (II) adhere to a communal mode of self-assembly; or (III) act to compromise the assembly of one another via incorporation and disruption. We find that a greater scope for controllable coassembly exists within orthogonal systems; which show minimal relative changes in the native gelator's supramolecular structure by Fourier transform infrared spectroscopy (FTIR), circular dichroism (CD), and fluorescence spectroscopy. This is indicative of the segregation of orthogonal coassembly constituents into distinct domains, where surfactant chemical functionality is presented at the surface of the gelator's supramolecular fibers. Overall, this work provides new insights into the design of modular coassembly systems, which have the potential to augment the chemical and physical properties of existing gelator systems. PMID:24568678

  15. Programming microenvironmental signals with bioactive peptide amphiphiles for skeletal and cardiac myogenesis

    OpenAIRE

    Garip, İmmihan Ceren

    2014-01-01

    Ankara : The Materials Science and Nanotechnology Program and the Graduate School of Engineering and Science of Bilkent University, 2014. Thesis (Master's) -- Bilkent University, 2014. Includes bibliographical references leaves 76-83. Garip, İmmihan Ceren Master's

  16. Electrostatic effects on the self-assembly mechanism of peptide amphiphiles

    OpenAIRE

    Toksöz, Sıla

    2010-01-01

    Ankara : The Graduate Program of Materials Science and Nanotechnology and the Institute of Engineering and Sciences of Bilkent University, 2010. Thesis (Master's) -- Bilkent University, 2010. Includes bibliographical references leaves 58-60. Toksöz, Sıla Master's

  17. Intestinal growth adaptation and glucagon-like peptide 2 in rats with ileal-jejunal transposition or small bowel resection

    DEFF Research Database (Denmark)

    Thulesen, Jesper; Hartmann, B.; Kissow, H.;

    2001-01-01

    Anatomy, glucagon-like peptide 2, small intestine, short bowel, intestinal adaptation, growth factors, rat......Anatomy, glucagon-like peptide 2, small intestine, short bowel, intestinal adaptation, growth factors, rat...

  18. 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.

  19. Electrochemical redox responsive polymeric micelles formed from amphiphilic supramolecular brushes.

    Science.gov (United States)

    Feng, Anchao; Yan, Qiang; Zhang, Huijuan; Peng, Liao; Yuan, Jinying

    2014-05-11

    The end-decorated homopolymer poly(ε-caprolactone)-ferrocene threaded onto a β-cyclodextrin-functionalized main-chain polymer can form a class of amphiphilic noncovalent graft copolymers based on the host-guest interactions of the terminal groups on the side chains. These new supramolecular polymer brushes can further self-assemble into micellar aggregates that exhibit reversible assembly and disassembly behavior under an electrochemical redox trigger, which opens up a new route to building dynamic block copolymer topologies. PMID:24681929

  20. From Vesicles to Protocells: The Roles of Amphiphilic Molecules

    Directory of Open Access Journals (Sweden)

    Yuka Sakuma

    2015-03-01

    Full Text Available It is very challenging to construct protocells from molecular assemblies. An important step in this challenge is the achievement of vesicle dynamics that are relevant to cellular functions, such as membrane trafficking and self-reproduction, using amphiphilic molecules. Soft matter physics will play an important role in the development of vesicles that have these functions. Here, we show that simple binary phospholipid vesicles have the potential to reproduce the relevant functions of adhesion, pore formation and self-reproduction of vesicles, by coupling the lipid geometries (spontaneous curvatures and the phase separation. This achievement will elucidate the pathway from molecular assembly to cellular life.

  1. From vesicles to protocells: the roles of amphiphilic molecules.

    Science.gov (United States)

    Sakuma, Yuka; Imai, Masayuki

    2015-01-01

    It is very challenging to construct protocells from molecular assemblies. An important step in this challenge is the achievement of vesicle dynamics that are relevant to cellular functions, such as membrane trafficking and self-reproduction, using amphiphilic molecules. Soft matter physics will play an important role in the development of vesicles that have these functions. Here, we show that simple binary phospholipid vesicles have the potential to reproduce the relevant functions of adhesion, pore formation and self-reproduction of vesicles, by coupling the lipid geometries (spontaneous curvatures) and the phase separation. This achievement will elucidate the pathway from molecular assembly to cellular life. PMID:25738256

  2. Identification of new members within suites of amphiphilic marine siderophores

    OpenAIRE

    Vraspir, Julia M.; Holt, Pamela D.; Butler, Alison

    2010-01-01

    Marine bacterial isolates Vibrio sp. HC0601C5 and Halomonas meridiana str. HC4321C1 were isolated off the coast of southern California and were found to produce an expanded suite of previously identified amphiphilic siderophores. Specifically two new members of the amphibactin family, amphibactins S and T, which have a C14:1 ω-7 fatty acid and a saturated C12 fatty acid, respectively, were produced by Vibrio sp. HC0601C5. These siderophores are produced in addition to a number of previously d...

  3. Synthesis of Amphiphilic Block Copolymers for Use in Biomedical Applications

    OpenAIRE

    Carmichael-Baranauskas, Anita Yvonne

    2010-01-01

    The research presented in this thesis focuses on the synthesis of three amphiphilic block copolymer systems containing poly(ethylene oxide) (PEO) blocks. The polymer systems were developed for use in biomedical applications. The first of these is a series of poly(ethylene oxide-b¬-oxazoline) (PEO-b-POX) diblock copolymers for use in the progress towards novel non-viral gene transfer vectors. Poly(ethylene oxide-b¬-2-ethyl-2-oxazoline) (PEO-b-PEOX) and poly(ethylene oxide-b¬-2-methyl-2-o...

  4. A Contact Angle Study of the Interaction between Embedded Amphiphilic Molecules and the PDMS Matrix in an Aqueous Environment

    Directory of Open Access Journals (Sweden)

    Wenjun Qiu

    2014-08-01

    Full Text Available Poly(dimethylsiloxane (PDMS surface modification via gradient-induced transport of embedded amphiphilic molecules is a novel, easy, flexible, and environmentally friendly approach for reducing protein adsorption on PDMS in microfluidic applications. To better understand the processing and the potential use in the viability-sensitive applications such as manipulation and culturing of primary neural cells, we systematically investigate how embedded molecules interact with a PDMS matrix and its surface in aqueous environments by studying the wetting angle over time under various processing conditions, including water exposure time, water exposure temperature, curing master materials, in addition to comparing different embedded amphiphilic molecules. The results indicate that the water exposure time clearly plays an important role in the surface properties. Our interpretation is that molecular rearrangement of the surface-embedded molecules improves surface coverage in the short term; while over a longer period, the transport of molecules embedded in the bulk enhance its coverage. However, this improvement finally terminates when molecules transported from the bulk to the surface are not sufficient to replace the molecules leaching into the water.

  5. Post-Translational Modifications in Secreted Peptide Hormones in Plants

    OpenAIRE

    Matsubayashi, Yoshikatsu

    2010-01-01

    More than a dozen secreted peptides are now recognized as important hormones that coordinate and specify cellular functions in plants. Recent evidence has shown that secreted peptide hormones often undergo post-translational modification and proteolytic processing, which are critical for their function. Such ‘small post-translationally modified peptide hormones’ constitute one of the largest groups of peptide hormones in plants. This short review highlights recent progress in research on post...

  6. Antimicrobial peptides.

    Science.gov (United States)

    Zhang, Ling-Juan; Gallo, Richard L

    2016-01-11

    Antimicrobial peptides and proteins (AMPs) are a diverse class of naturally occurring molecules that are produced as a first line of defense by all multicellular organisms. These proteins can have broad activity to directly kill bacteria, yeasts, fungi, viruses and even cancer cells. Insects and plants primarily deploy AMPs as an antibiotic to protect against potential pathogenic microbes, but microbes also produce AMPs to defend their environmental niche. In higher eukaryotic organisms, AMPs can also be referred to as 'host defense peptides', emphasizing their additional immunomodulatory activities. These activities are diverse, specific to the type of AMP, and include a variety of cytokine and growth factor-like effects that are relevant to normal immune homeostasis. In some instances, the inappropriate expression of AMPs can also induce autoimmune diseases, thus further highlighting the importance of understanding these molecules and their complex activities. This Primer will provide an update of our current understanding of AMPs. PMID:26766224

  7. 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.

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

    Science.gov (United States)

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

    2013-08-01

    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.

  9. Amphiphilic biopolymers (amphibiopols) as new surfactants for membrane protein solubilization

    Science.gov (United States)

    Duval-Terrié, Caroline; Cosette, Pascal; Molle, Gérard; Muller, Guy; Dé, Emmanuelle

    2003-01-01

    The aim of this study was to develop new surfactants for membrane protein solubilization, from a natural, biodegradable polymer: the polysaccharide pullulan. A set of amphiphilic pullulans (HMCMPs), differing in hydrophobic modification ratio, charge ratio, and the nature of the hydrophobic chains introduced, were synthesized and tested in solubilization experiments with outer membranes of Pseudomonas fluorescens. The membrane proteins were precipitated, and then resolubilized with various HMCMPs. The decyl alkyl chain (C10) was the hydrophobic graft that gave the highest level of solubilization. Decyl alkyl chain-bearing HMCMPs were also able to extract integral membrane proteins from their lipid environment. The best results were obtained with an amphiphilic pullulan bearing 18% decyl groups (18C10). Circular dichroism spectroscopy and membrane reconstitution experiments were used to test the structural and functional integrity of 18C10-solubilized proteins (OmpF from Escherichia coli and bacteriorhodopsin from Halobacterium halobium). Whatever their structure type (α or β), 18C10 did not alter either the structure or the function of the proteins analyzed. Thus, HMCMPs appear to constitute a promising new class of polymeric surfactants for membrane protein studies. PMID:12649425

  10. DEFORMATION OF COPOLYMER MICELLES INDUCED BY AMPHIPHILIC DIMER PARTICLES

    Institute of Scientific and Technical Information of China (English)

    Xiao-chun Qin; Chun-lai Ren

    2012-01-01

    Combining self-consistent-field theory and density-functional theory,we systematically study the deformation of copolymer micelles induced by the presence of amphiphilic dimer particles.Due to the amphiphilic nature,dimer particles tend to accumulate onto the interface of the copolymer micelle.With increasing concentration of the symmetric dimer particles,which are made of two identical spherical particles,the micelle deforms from the initial sphere to ellipse,dumbbell,and finally separates into two micelles.Furthermore,asymmetric dimer particles,composed by two particles with different sizes,are considered to investigate the influence of geometry of dimer particles on the deformation of the micelle.It is found that the micelle inclines to deform into dumbbell due to the additional curvature originating in the gathering of asymmetric dimer particles onto the interface of the micelle.The present study on the deformation of micelles is useful to understand the possible shape variation in the course of cell division/fusion.

  11. Lipophosphoramidate-based bipolar amphiphiles: their syntheses and transfection properties.

    Science.gov (United States)

    Berchel, Mathieu; Le Gall, Tony; Lozach, Olivier; Haelters, Jean-Pierre; Montier, Tristan; Jaffrès, Paul-Alain

    2016-03-14

    Six new cationic bolaamphiphiles (also called bipolar amphiphiles, bolaform amphiphiles, or bolalipids) were readily prepared by a thiol-ene click reaction that engaged a mercapto-alcohol (mercapto-ethanol or mercapto-hexanol) and a cationic based lipophosphoramidate. The cationic lipophosphoramidates contain two lipid chains that end in an alkene group and a selected cationic polar head group (trimethylammonium, dimethyl hydroxyethyl ammonium, or methylimidazolium). These compounds were formulated in water (with or without DOPE as a colipid) to produce supramolecular aggregates. These aggregates, before (i.e. bolasomes) and after (i.e. bolaplexes) mixing with plasmid DNA (pDNA) at various charge ratios, were characterized with regard to their sizes and zeta potentials. In the case of bolasomes, the suspensions were unstable since precipitation occurred after only a few hours at room temperature. On the other hand, bolaplex formulations exhibited clearly a better colloidal stability. Then, the gene delivery properties of the cationic bolasomes were investigated using two human-derived epithelial cell lines (A549 and 16HBE). Compared to the commercially available lipofection reagent (Lipofectamine), most of the cationic bolaamphiphiles were able to efficiently transfect these cells when they were formulated with DOPE in a 1 : 1 molar ratio. We report herein that bolaamphiphiles possessing a trimethylammonium or a dimethyl hydroxyethyl ammonium head group were the most efficient in terms of transfection efficiency while exhibiting no significant cytotoxicity. PMID:26864681

  12. The Behavior of Amphiphile at Oil-Water Interface by Monte Carlo Simulation%双亲分子在油水界面的行为研究

    Institute of Scientific and Technical Information of China (English)

    潘海华; 李啸风; 李浩然; 刘迪霞; 韩世钧

    2003-01-01

    A novel simple two-dimensional square-lattice model of amphiphile at oil-water interface is developed,in which oil and water act as solvent and occupy empty sites and amphiphile occupies chains of sites. In thismodel, the oil-water interface is fixed, And amphiphile molecules will be enriched at the oil-water interface. Theinterfacial concentration of amphiphile calculated by Monte Carlo method shows that it is easier for the hydrophilic-hydrophobic balanced amphiphile to stay at the interface. And the adsorption of amphiphile increases with theincrease of amphiphile concentration and the decrease with temperature.

  13. Self-Assembled Proteins and Peptides as Scaffolds for Tissue Regeneration.

    Science.gov (United States)

    Loo, Yihua; Goktas, Melis; Tekinay, Ayse B; Guler, Mustafa O; Hauser, Charlotte A E; Mitraki, Anna

    2015-11-18

    Self-assembling proteins and peptides are increasingly gaining interest for potential use as scaffolds in tissue engineering applications. They self-organize from basic building blocks under mild conditions into supramolecular structures, mimicking the native extracellular matrix. Their properties can be easily tuned through changes at the sequence level. Moreover, they can be produced in sufficient quantities with chemical synthesis or recombinant technologies to allow them to address homogeneity and standardization issues required for applications. Here. recent advances in self-assembling proteins, peptides, and peptide amphiphiles that form scaffolds suitable for tissue engineering are reviewed. The focus is on a variety of motifs, ranging from minimalistic dipeptides, simplistic ultrashort aliphatic peptides, and peptide amphiphiles to large "recombinamer" proteins. Special emphasis is placed on the rational design of self-assembling motifs and biofunctionalization strategies to influence cell behavior and modulate scaffold stability. Perspectives for combination of these "bottom-up" designer strategies with traditional "top-down" biofabrication techniques for new generations of tissue engineering scaffolds are highlighted. PMID:26461979

  14. Synthesis of Polymerizable Amphiphiles with Systematic Variation of Critical Packing Parameters

    Institute of Scientific and Technical Information of China (English)

    M. H. Li; W. L. Yang; J. Qian; C. C. Wang; S. K. Fu

    2005-01-01

    @@ 1Introduction An amphiphile is a molecule composed of hydrophilic part and hydrophobic part, which are incompatible and tend to separate from each other. The tendency of separation is often promoted by addition of water and sometimes also oil. Under balanced conditions the mixtures form macroscopically homogeneous phases, including isotropic solution phases and liquid crystalline phases. Correlation of the amphiphile structure with its preferred phases could be understood with a simple geometric model[1], which defines a dimensionless Critical Packing Parameter (CPP) to describe the relative bulkiness of the hydrophobic part and the hydrophilic part in an amphiphile. With CPP increasing from a small value to a high value the amphiphile changes from hydrophilic to hydrophobic, its preferred phase structure from direct structures via lamellar structure to reverse structures. This model provides a basis for the molecular design of amphiphiles. To immobilize the microstructure of the phases formed by amphiphiles is a challenge for current material chemists. Techniques of both inorganic polymerization[2] and organic polymerization[3] have been developed. With organic polymerization the molecular design of polymerizable amphiphiles is critical for the successful immobilization of the vulnerable precursor microstructures.

  15. Electron paramagnetic resonance study of amphiphiles partitioning behavior in desiccation-tolerant moss during dehydration

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Desiccation tolerance is a crucial characteristic for desert moss surviving in arid regions. Desiccation procedure always induces amphiphiles transferring from the polar cytoplasm into lipid bodies. The behavior of amphiphiles transferring can contribute to the enhancement of desiccation tolerance and the reduction of plasma membrane integrity simultaneously. The effects of amphiphiles partitioning into the lipid phase during water loss has been studied for pollen and seeds using electron paramagnetic resonance (EPR) spectroscopy. However, desiccation-tolerant high plants occur among mosses, several angiosperms and higher plants seeds or pollens. They have different strategies for survival in dehydration and rehydration. A desiccation-tolerant moss Tortula desertorurn was used to investigate the behaviors of amphiphilic molecules during drying by spin label technology. There are small amount of amphiphilic probes partitioning into membrane during moss leaves dehydration, comparing with that in higher plants. Cytoplasm viscosity changed from 1.14 into glass state only dehydration less than 60 min. Moss leaves lost plasma membrane integrity slightly,from 0.115 to 0.237, occurred simultaneously with amphiphiles partition. The results showed the more advantages of mosses than higher plants in adapting fast dehydration. We propose that EPR spin label is feasible for studying the amphiphiles partitioning mechanisms in membrane protection and damage for desiccation-tolerant mosses.(C) 2007 Yan Wang. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

  16. Self-assembly of phosphate amphiphiles in mixtures of prebiotically plausible surfactants.

    Science.gov (United States)

    Albertsen, A N; Duffy, C D; Sutherland, J D; Monnard, P-A

    2014-06-01

    The spontaneous formation of closed bilayer structures from prebiotically plausible amphiphiles is an essential requirement for the emergence of early cells on prebiotic Earth. The sources of amphiphiles could have been both endo- and exogenous (accretion of meteorite carbonaceous material or interstellar dust particles). Among all prebiotic possible amphiphile candidates, those containing phosphate are the least investigated species because their self-assembly occurs in a seemingly too narrow range of conditions. The self-assembly of simple phosphate amphiphiles should, however, be of great interest, as contemporary membranes predominantly contain phospholipids. In contrast to common expectations, we show that these amphiphiles can be easily synthesized under prebiotically plausible environmental conditions and can efficiently form bilayer structures in the presence of various co-surfactants across a large range of pH values. Vesiculation was even observed in crude reaction mixtures that contained 1-decanol as the amphiphile precursor. The two best co-surfactants promoted vesicle formation over the entire pH range in aqueous solutions. Expanding the pH range where bilayer membranes self-assemble and remain intact is a prerequisite for the emergence of early cell-like compartments and their preservation under fluctuating environmental conditions. These mixed bilayers also retained small charged solutes, such as dyes. These results demonstrate that alkyl phosphate amphiphiles might have played a significant role as early compartment building blocks.

  17. 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....

  18. Cucurbit[7]uriI-Based Vesicles Formed by Self-assembly of Supramolecular Amphiphiles

    Institute of Scientific and Technical Information of China (English)

    李佳锡; 周黎鹏; 罗全; 王永国; 张春秋; 卢伟; 徐家云; 刘俊秋

    2012-01-01

    Cucurbituril (CB), a well-known macrocyclic cavitand, has been used extensively to construct supramolecular aggregates. Based on host-guest intertactions, an adamantanyl derivative guest molecule was designed and syn- thesized to prepare a supramolecular amphiphile with cucurbit[7]uril. In aqueous solution, the cucurbit[7]uril based supramolecular amphiphiles self-assemble into well-defined vesicles, and their disassembly can be achieved by addition of excess competitive agent 1-adamantanamine hydrochloride. This vesicle functions as a new nanocapsule to encapsulate molecules within its hollow cavity. Through competitive disassembly of supramolecular amphiphiles, the vesicles behave as a novel drug delivery carrier.

  19. Syntheses, Characterization, Physical and Biological Properties of Long-chain, Water-soluble, Dendritic Amphiphiles

    OpenAIRE

    Williams, André Arvin

    2008-01-01

    In this project, we have designed and synthesized a new series of long-chain, water-soluble, dendritic, anionic amphiphiles [3CAmn, RCONHC(CH2CH2COOH)3, R= CnH2n+1] to alleviate the low aqueous solubility of fatty acids. The dendritic-tricarboxlyato headgroup improves aqueous solubility and allows us to measure the intrinsic biological activity of our amphiphiles without the potential hindrance of low aqueous solubility. The aqueous solubilities of the anionic amphiphiles have been measured...

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

    OpenAIRE

    Bandi, Mahesh; Goldburg, Walter; Cressman Jr., John; Kellay, Hamid

    2006-01-01

    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 $\\mu$m 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 ...

  1. Large-scale dissipative particle dynamics simulations of self-assembly amphiphilic systems†

    Science.gov (United States)

    Li, Xuejin; Tang, Yu-Hang

    2014-01-01

    We present large-scale simulation results on the self-assembly of amphiphilic systems in bulk solution and under soft confinement. Self-assembled unilamellar and multilamellar vesicles are formed from amphiphilic molecules in bulk solution. The system is simulated by placing amphiphilic molecules inside large unilamellar vesicles (LUVs) and the dynamic soft confinement-induced self-assembled vesicles are investigated. Moreover, the self-assembly of sickle hemoglobin (HbS) is simulated in a crowded and fluctuating intracellular space and our results demonstrate that the HbS self-assemble into polymer fibers causing the LUV shape to be distorted. PMID:24938634

  2. Amphiphilic organosilane-directed synthesis of crystalline zeolite with tunable mesoporosity.

    Science.gov (United States)

    Choi, Minkee; Cho, Hae Sung; Srivastava, Rajendra; Venkatesan, Chithravel; Choi, Dae-Heung; Ryoo, Ryong

    2006-09-01

    Zeolites are a family of crystalline aluminosilicate materials widely used as shape-selective catalysts, ion exchange materials, and adsorbents for organic compounds. In the present work, zeolites were synthesized by adding a rationally designed amphiphilic organosilane surfactant to conventional alkaline zeolite synthesis mixtures. The zeolite products were characterized by a complementary combination of X-ray diffraction (XRD), nitrogen sorption, scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The analyses show that the present method is suitable as a direct synthesis route to highly mesoporous zeolites. The mesopore diameters could be uniformly tailored, similar to ordered mesoporous silica with amorphous frameworks. The mesoporous zeolite exhibited a narrow, small-angle XRD peak, which is characteristic of the short-range correlation between mesopores, similar to disordered wormhole-like mesoporous materials. The XRD patterns and electron micrographs of the samples taken during crystallization clearly showed the evolution of the mesoporous structure concomitantly to the crystallization of zeolite frameworks. The synthesis of the crystalline aluminosilicate materials with tunable mesoporosity and strong acidity has potentially important technological implications for catalytic reactions of large molecules, whereas conventional mesoporous materials lack hydrothermal stability and acidity. PMID:16892049

  3. A novel pyrene-based fluorescing amphiphile with unusual bulk and interfacial properties.

    Science.gov (United States)

    Salonen, Anniina; Knyazev, Anton; von Bandel, Nicolas; Degrouard, Jéril; Langevin, Dominique; Drenckhan, Wiebke

    2011-01-17

    We have synthesised a new, pyrene-based, low-molecular-mass, amphiphilic molecule that displays a wealth of properties of potential interest for aggregation and interfacial applications. In order to elucidate some of the key properties of this molecule, which consists of a pyrene-containing hydrophobic head and a short PEG-based hydrophilic tail, we investigate herein some aspects of its concentration-dependent behaviour in aqueous solutions. We show that the inclusion of the hydrophobic pyrene group not only provides the molecule with intriguing bulk and interfacial properties down to low concentrations, but also with various means of assessing its aggregation behaviour by means of its well-characterised fluorescence properties. Combining a range of fluorescence techniques with microscopic imaging (optical and Cryo-TEM), interfacial tension measurements and foaming studies, we have been able to identify and characterise three concentration-dependant regimes. At low concentrations, the molecule is dissolved in monomeric form. At intermediate concentrations, labile aggregates are formed, which, at higher concentrations, give way to aggregates containing pre-associated pyrenes. Our measurements strongly imply that the latter aggregates are hexagonally close-packed tubular micelles. In this latter regime we also find a range of micron-sized precipitates. Additionally, the molecule displays strong interfacial activity, yet a surprisingly slow dynamics of interfacial adsorption. Finally, we demonstrate the possibility of using it to visualize interfaces and also create reasonably stable (1 hour) and fluorescing foams. PMID:21226196

  4. Preparation of Chiral 1,4-Phenylene-silicas via Chiral Low-molecular-weight Amphiphiles

    Institute of Scientific and Technical Information of China (English)

    XIAO Min; LIU Xiao-juan; HU Kai; WU Li-min; LI Yi; LI Bao-zong; YANG Yong-gang

    2012-01-01

    Chiral organic-inorganic hybrid silicas can be prepared via the self-assemblies of chiral surfactants and gelators as templates.However,the relationship between the chirality of the hybrid silica and the structure of the surfactant/gelator has not been systemically studied.Herein,a series of chiral low-molecular-weight amphiphiles(LMWAs) derived from L-valine was synthesized.Their alkyl chains were n-butadecyl,n-hexadecyl and n-octadecyl,respectively.They can form viscous liquids in pure water,and physical gels in tetrahydrofuran,cyclohexanone,acetonitrile,acetone,chlorobenzene and nitrobenzenc.Chiral 1,4-phenylene-silicas were prepared via the self-assemblies of these LMWAs as templates.With increasing the alkyl chain length,the 1,4-phenylene-silicas changed from short mesoporous nanorods to long nanotubcs. The circular dichroism spectra of the 1,4-phenylene-silicas indicated that the long nanotubes exhibit the strongest chirality.

  5. Self-assembled cationic peptide nanoparticles as an efficient antimicrobial agent

    Science.gov (United States)

    Liu, Lihong; Xu, Kaijin; Wang, Huaying; Jeremy Tan, P. K.; Fan, Weimin; Venkatraman, Subbu S.; Li, Lanjuan; Yang, Yi-Yan

    2009-07-01

    Antimicrobial cationic peptides are of interest because they can combat multi-drug-resistant microbes. Most peptides form α-helices or β-sheet-like structures that can insert into and subsequently disintegrate negatively charged bacterial cell surfaces. Here, we show that a novel class of core-shell nanoparticles formed by self-assembly of an amphiphilic peptide have strong antimicrobial properties against a range of bacteria, yeasts and fungi. The nanoparticles show a high therapeutic index against Staphylococcus aureus infection in mice and are more potent than their unassembled peptide counterparts. Using Staphylococcus aureus-infected meningitis rabbits, we show that the nanoparticles can cross the blood-brain barrier and suppress bacterial growth in infected brains. Taken together, these nanoparticles are promising antimicrobial agents that can be used to treat brain infections and other infectious diseases.

  6. Antimicrobial Peptide-Driven Colloidal Transformations in Liquid-Crystalline Nanocarriers.

    Science.gov (United States)

    Gontsarik, Mark; Buhmann, Matthias T; Yaghmur, Anan; Ren, Qun; Maniura-Weber, Katharina; Salentinig, Stefan

    2016-09-01

    Designing efficient colloidal systems for the delivery of membrane active antimicrobial peptides requires in-depth understanding of their structural and morphological characteristics. Using dispersions of inverted type bicontinuous cubic phase (cubosomes), we examine the effect of integrating the amphiphilic peptide LL-37 at different concentrations on the self-assembled structure and evaluate its bactericidal ability against Escherichia coli. Small-angle X-ray scattering, dynamic light scattering, and cryogenic transmission electron microscopy show that LL-37 integrates into the bicontinuous cubic structure, inducing colloidal transformations to sponge and lamellar phases and micelles in a concentration-dependent manner. These investigations, together with in vitro evaluation studies using a clinically relevant bacterial strain, established the composition-nanostructure-activity relationship that can guide the design of new nanocarriers for antimicrobial peptides and may provide essential knowledge on the mechanisms underlying the bacterial membrane disruption with peptide-loaded nanostructures. PMID:27541048

  7. Semi-wet peptide/protein array using supramolecular hydrogel

    Science.gov (United States)

    Kiyonaka, Shigeki; Sada, Kazuki; Yoshimura, Ibuki; Shinkai, Seiji; Kato, Nobuo; Hamachi, Itaru

    2004-01-01

    The protein microarray is a crucial biomaterial for the rapid and high-throughput assay of many biological events where proteins are involved. In contrast to the DNA microarray, it has not been sufficiently established because of protein instability under the conventional dry conditions. Here we report a novel semi-wet peptide/protein microarray using a supramolecular hydrogel composed of glycosylated amino acetate. The spontaneous gel-formation and amphiphilic properties of this supramolecular hydrogel have been applied to a new type of peptide/protein gel array that is compatible with enzyme assays. Aqueous cavities created in the gel matrix are a suitable semi-wet reaction medium for enzymes, whereas the hydrophobic domains of the fibre are useful as a unique site for monitoring the reaction. This array system overcomes several drawbacks of conventional protein chips, and thus can have potential applications in pharmaceutical research and diagnosis.

  8. Perfluorinated Moieties Increase the Interaction of Amphiphilic Block Copolymers with Lipid Monolayers.

    Science.gov (United States)

    Schwieger, Christian; Blaffert, Jacob; Li, Zheng; Kressler, Jörg; Blume, Alfred

    2016-08-16

    The interaction of amphiphilic and triphilic block copolymers with lipid monolayers has been studied. Amphiphilic triblock copolymer PGMA20-PPO34-PGMA20 (GP) is composed of a hydrophobic poly(propylene oxide) (PPO) middle block that is flanked by two hydrophilic poly(glycerol monomethacrylate) (PGMA) side blocks. The attachment of a perfluoro-n-nonyl residue (F9) to either end of GP yields a triphilic polymer with the sequence F9-PGMA20-PPO34-PGMA20-F9 (F-GP). The F9 chains are fluorophilic, i.e., they have a tendency to demix in hydrophilic as well as in lipophilic environments. We investigated (i) the adsorption of both polymers to differently composed lipid monolayers and (ii) the compression behavior of mixed polymer/lipid monolayers. The lipid monolayers are composed of phospholipids with PC or PE headgroups and acyl chains of different length and saturation. Both polymers interact with lipid monolayers by inserting their hydrophobic moieties (PPO, F9). The interaction is markedly enhanced in the presence of F9 chains, which act as membrane anchors. GP inserts into lipid monolayers up to a surface pressure of 30 mN/m, whereas F-GP inserts into monolayers at up to 45 mN/m, suggesting that F-GP also inserts into lipid bilayer membranes. The adsorption of both polymers to lipid monolayers with short acyl chains is favored. Upon compression, a two-step squeeze-out of F-GP occurs, with PPO blocks being released into the aqueous subphase at 28 mN/m and the F9 chains being squeezed out at 48 mN/m. GP is squeezed out in one step at 28 mN/m because of the lack of F9 anchor groups. The liquid expanded (LE) to liquid condensed (LC) phase transition of DPPC and DMPE is maintained in the presence of the polymers, indicating that the polymers can be accommodated in LE- and LC-phase monolayers. These results show how fluorinated moieties can be included in the rational design of membrane-binding polymers. PMID:27442444

  9. The crystal structure of the calcium-bound con-G[Q6A] peptide reveals a novel metal-dependent helical trimer

    OpenAIRE

    Cnudde, Sara E.; Prorok, Mary; Jia, Xaofei; Castellino, Francis J.; Geiger, James H.

    2010-01-01

    The ability to form and control both secondary structure and oligomerization in short peptides has proven to be challenging due to the structural instability of such peptides. The conantokin peptides are a family of gamma-carboxy-glutamic acid containing peptides produced in the venoms of predatory sea snails of the conus family. They are examples of short peptides that form stable helical structures, especially in the presence of divalent cations. Both monomeric and dimeric conantokin peptid...

  10. Bulk modification of PDMS microchips by an amphiphilic copolymer.

    Science.gov (United States)

    Xiao, Yan; Yu, Xiao-Dong; Xu, Jing-Juan; Chen, Hong-Yuan

    2007-09-01

    A simple and rapid bulk-modification method based on adding an amphiphilic copolymer during the fabrication process was employed to modify PDMS microchips. Poly(lactic acid)-poly(ethylene glycol) (PLA-PEG) was used as the additive substance. Compared to the native PDMS microchips, both the contact angle and the EOF of the bulk-modified PDMS microchips decreased. The effects of the additive loading and the pH on the EOF were investigated in detail. The bulk-modified PDMS microchips exhibited reproducible and stable EOF behavior. The application of the bulk-modified PDMS microchips was also studied and the results indicated that they could be successfully used to separate amino acids and to suppress protein adsorption.

  11. Structure and reactivity in amphiphile-water micelles

    International Nuclear Information System (INIS)

    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)

  12. Amphiphilic siderophore production by oil-associating microbes.

    Science.gov (United States)

    Kem, Michelle P; Zane, Hannah K; Springer, Stephen D; Gauglitz, Julia M; Butler, Alison

    2014-06-01

    The Deepwater Horizon oil spill in 2010 released an unprecedented amount of oil into the ocean waters of the Gulf of Mexico. As a consequence, bioremediation by oil-degrading microbes has been a topic of increased focus. One factor limiting the rate of hydrocarbon degradation by microbial communities is the availability of necessary nutrients, including iron. The siderophores produced from two Vibrio spp. isolated from the Gulf of Mexico following the Deepwater Horizon oil spill, along with the well-studied oil-degrading microbe, Alcanivorax borkumensis SK2, are studied under iron-limiting conditions. Here we report the amphiphilic amphibactin siderophores produced by the oil-associated bacteria, Vibrio sp. S1B, Vibrio sp. S2A and Alcanivorax borkumensis SK2. These findings provide insight into oil-associating microbial iron acquisition. PMID:24663669

  13. 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.

  14. 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. PMID:27472455

  15. Non-Surface Activity of Cationic Amphiphilic Diblock Copolymers

    Energy Technology Data Exchange (ETDEWEB)

    Nayak, Rati Ranjan; Yamada, Tasuku; Matsuoka, Hideki, E-mail: ratiranjan@immt.res.in, E-mail: matsuoka@star.polym.kyoto-u.ac.jp [Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Nishikyo-ku, Kyoto 615-8510 (Japan)

    2011-09-19

    Cationic amphiphilic diblock copolymers containing quaternized poly (2-vinylpyridine) chain as a hydrophilic segment (PIp-b-PNMe2VP) were synthesized by living anionic polymerization. By IR measurement, we confirmed the quaternization of the polymer (PIp-b-PNMe2VP), and determined the degree of quaternization by conductometric titration. The surface tension experiment showed that the polymers are non-surface active in nature. The foam formation of the polymer solutions was also investigated with or without added salt. Almost no foam formation behavior was observed without added salt, while a little foam was observed in the presence of 1M NaCl. The critical micelle concentration (cmc) of the diblock copolymers with 3 different chain lengths was measured by the static light scattering method. The cmc values obtained in this study were much lower than the values obtained for anionic non-surface active diblock polymers studied previously. The hydrodynamic radii of the polymer micelle increased slightly in the presence of 1 M NaCl. The transmission electron microscopic images revealed spherical micelles in pure water. In the presence of salt, the cmc values increased as was the case for anionic polymers, which is unlike conventional surfactant systems but consistent with non-surface active anionic block copolymers. The microviscosity of the micelle core was evaluated using Coumarin-153 as a fluorescent anisotropy probe using steady-sate fluorescence depolarization. Non-surface activity has been proved to be universal for ionic amphiphilic block copolymers both for anionic and cationic. Hence, the origin of non-surface activity is not the charged state of water surface itself, but should be an image charge repulsion at the air/water interface.

  16. Globules of annealed amphiphilic copolymers: Surface structure and interactions

    Science.gov (United States)

    Jarkova, E.; Johner, A.; Maresov, E. A.; Semenov, A. N.

    2006-12-01

    A mean-field theory of globules of random amphiphilic copolymers in selective solvents is developed for the case of an annealed copolymer sequence: each unit can be in one of two states, H (insoluble) or P (soluble or less insoluble). The study is focussed on the regime when H and P units tend to form long blocks, and when P units dominate in the dilute phase, but are rare in the globule core. A first-order coil-to-globule transition is predicted at some T = Tcg. The globule core density at the transition point increases as the affinity of P units to the solvent, tildeɛ, is increased. Two collapse transitions, coil → “loose” globule and “loose” globule → “dense” globule, are predicted if tildeɛ is high enough and P units are marginally soluble or weakly insoluble. H and P concentration profiles near the globule surface are obtained and analyzed in detail. It is shown that the surface excess of P units rises as tildeɛ is increased. The surface tension decreases in parallel. Considering the interaction between close enough surfaces of two globules, we show that they always attract each other at a complete equilibrium. It is pointed out, however, that such equilibrium may be difficult to reach, so that partially equilibrium structures (defined by the condition that a chain forming one globule does not penetrate into the core of the other globule) are relevant. It is shown that at such partial equilibrium the interaction is repulsive, so the globules may be stabilized from aggregation. The strongest repulsion is predicted at the coil-to-globule transition point Tcg: the repulsion force decreases with the distance between the surfaces according to a power law. In the general case (apart from Tcg) the force vs. distance decay becomes exponential; the decay length ξ diverges as T → Tcg. The developed theory explains certain anomalous properties observed for globules of amphiphilic homopolymers.

  17. Peptide Vaccine: Progress and Challenges

    Directory of Open Access Journals (Sweden)

    Weidang Li

    2014-07-01

    Full Text Available Conventional vaccine strategies have been highly efficacious for several decades in reducing mortality and morbidity due to infectious diseases. The bane of conventional vaccines, such as those that include whole organisms or large proteins, appear to be the inclusion of unnecessary antigenic load that, not only contributes little to the protective immune response, but complicates the situation by inducing allergenic and/or reactogenic responses. Peptide vaccines are an attractive alternative strategy that relies on usage of short peptide fragments to engineer the induction of highly targeted immune responses, consequently avoiding allergenic and/or reactogenic sequences. Conversely, peptide vaccines used in isolation are often weakly immunogenic and require particulate carriers for delivery and adjuvanting. In this article, we discuss the specific advantages and considerations in targeted induction of immune responses by peptide vaccines and progresses in the development of such vaccines against various diseases. Additionally, we also discuss the development of particulate carrier strategies and the inherent challenges with regard to safety when combining such technologies with peptide vaccines.

  18. Current trends in the clinical development of peptide therapeutics.

    Science.gov (United States)

    Saladin, Pauline M; Zhang, Bodi D; Reichert, Janice M

    2009-12-01

    The development of peptides as drugs is attracting increasing attention from the pharmaceutical industry. This interest is at least partially a consequence of the widespread acceptance of therapeutic proteins by physicians and patients, and because of improvements to problems such as a short half-life and delivery issues. The markets for peptide-based compounds can be substantial, with six peptide drugs attaining global sales of more than US $750 million in 2008. To track trends in the clinical development and marketing approval of peptides, Tufts Center for the Study of Drug Development and Ferring Research Institute compiled publically available data for peptides that entered clinical trials sponsored by commercial firms, with a focus on peptide therapeutics, but also including peptide vaccines and diagnostics. The results provide an historical overview of the development of peptide therapeutics, and may inform strategic planning in this area.

  19. Nucleoside, nucleotide and oligonucleotide based amphiphiles: a successful marriage of nucleic acids with lipids.

    Science.gov (United States)

    Gissot, Arnaud; Camplo, Michel; Grinstaff, Mark W; Barthélémy, Philippe

    2008-04-21

    Amphiphilic molecules based on nucleosides, nucleotides and oligonucleotides are finding more and more biotechnological applications. This Perspective highlights their synthesis, supramolecular organization as well as their applications in the field of biotechnology.

  20. 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......Many drugs are amphiphiles that, in addition to binding to a particular target protein, adsorb to cell membrane lipid bilayers and alter intrinsic bilayer physical properties (e. g., bilayer thickness, monolayer curvature, and elastic moduli). Such changes can modulate membrane protein function......-B) that summarizes the bilayer elastic properties, as sensed by a bilayer-spanning protein. Amphiphile-induced changes in H-B, measured using gA channels of a particular length, quantitatively predict changes in lifetime for channels of a different length-as well as changes in the inactivation of voltage...

  1. Amphiphilic organoplatinum(II) complexes: Self-assembly in solution and at interfaces

    Science.gov (United States)

    Maran, Umamageswaran

    Organoplatinum(II) gemini amphiphiles with three different chain lengths and a predefined angle of 60° are synthesized. Self-organization at the air-water interface is investigated as a function of chain length and reduction in surface area, by using Langmuir-trough techniques. The atomic force microscopy (AFM) images of the transferred Langmuir-Schaefer (LS) films reveals wormlike aggregates for the organoplatinum(II) gemini amphiphiles, possessing hexyloxy- and dodecyloxy-chains. A neutral crown ether functionalized [1+1] facial amphiphile was self-assembled from a flexible 32-membered dibenzo crown ether and a diplatinum acceptor clip. A homologous series of charged triangle-shaped amphiphilic metallomacrocyles was self-assembled from stoichiometric amounts of organoplatinum(II) gemini amphiphiles and bipyridyl donor molecules in quantitative yields. The amphiphilic triangular scaffolds were characterized by multinuclear NMR and ESI-MS. A new amphiphilic organoplatinum(II) precursor with a predefined angle of 90° was synthesized. The precursor was mixed in stoichiometric ratios with two different 3-substituted pyridines and a rigid bipyridyl ligand to construct three charged amphiphilic metallomacrocyles. The computational calculations on the assemblies constructed from flexible 3-substituted pyridines indicate that the assemblies exist largely as chair isomers. The self-organization of the hexacationic triangular amphiphiles at liquid-liquid, air-water and solid-air interfaces was studied using confocal microscopy, in situ Raman spectroscopy, Langmuir-trough techniques, fluorescence spectroscopy and AFM. The amphiphilic triangle with octadecyloxy-chains was found to form a bicontinuous coacervate with pores in a chloroform/water solvent mixture. The pressure-area isotherms revealed formation of surface aggregates at the air-water interface. Fluid AFM studies on the transferred LS layers reveal ridge-like patterns with a flat top. Models were constructed to

  2. Amphiphilic oligoethyleneimine-β-cyclodextrin "click" clusters for enhanced DNA delivery.

    Science.gov (United States)

    Martínez, Álvaro; Bienvenu, Céline; Jiménez Blanco, José L; Vierling, Pierre; Mellet, Carmen Ortiz; García Fernández, José M; Di Giorgio, Christophe

    2013-08-16

    Monodisperse amphiphilic oligoethyleneimine (OEI)-β-cyclodextrin (βCD) clusters have been prepared, and their potential as gene delivery systems has been evaluated in comparison with a nonamphiphilic congener. The general prototype incorporates tetraethyleneimine segments linked to the primary rim of βCD through either triazolyl or thioureidocysteaminyl connectors. Transfection efficiency data for the corresponding CD:pDNA nanocomplexes (CDplexes) in BNL-CL2 murine hepatocytes evidenced the strong beneficial effect of facial amphiphilicity. PMID:23859761

  3. Synthesis and aggregation properties of amphiphilic mono and bisadducts of fullerene in aqueous solution

    Institute of Scientific and Technical Information of China (English)

    Pu Zhang; Zhi Xin Guo; Shuang Lv

    2008-01-01

    New amphiphilic[60]fullerene monoadduet TPF and bisadducts BTPF were synthesized and well-characterized. Their aggregation properties in aqueous solution was investigated by UV-vis and TEM methods. In aqueous solution, monoadduct TPF forms irregularly shaped and some rod-like aggregates, whereas bisadducts BTPF gives spherical aggregates with diameters of 50-150 nm. It indicated that the aggregation properties of amphiphilic fullerene derivatives depend on the number of hydrophilic appendage on the C60 cage.

  4. SYNTHESIS OF AMPHIPHILIC COMB-SHAPED COPOLYMERS USED FOR SURFACE MODIFICATION OF PVDF MEMBRANES

    Institute of Scientific and Technical Information of China (English)

    徐又一

    2009-01-01

    The synthesis of a novel amphiphilic comb-shaped copolymer consisting of a main chain of styrene-(N-(4- hydroxyphenyl) maleimide)(SHMI) copolymer and poly(ethylene glycol) methyl ether methacrylate(PEGMA) side groups was achieved by atom transfer radical polymerization(ATRP).The amphiphilic copolymers were characterized by ~1H-NMR, Fourier transform infrared(FTIR) spectroscopy and gel permeation chromatography(GPC).From thermogravimetric analysis (TGA),the decomposition temperature of SHMI-g-PEGMA is low...

  5. Amphiphile self-assemblies in supercritical CO2 and ionic liquids.

    Science.gov (United States)

    Zhang, Jianling; Peng, Li; Han, Buxing

    2014-08-28

    Supercritical (sc) CO2 and ionic liquids (ILs) are very attractive green solvents with tunable properties. Using scCO2 and ILs as alternatives of conventional solvents (water and oil) for forming amphiphile self-assemblies has many advantages. For example, the properties and structures of the amphiphile self-assemblies in these solvents can be easily modulated by tuning the properties of solvents; scCO2 has excellent solvation power and mass-transfer characteristics; ILs can dissolve both organic and inorganic substances and their properties are designable to satisfy the requirements of various applications. Therefore, the amphiphile self-assemblies in scCO2 and ILs have attracted considerable attention in recent years. This review describes the advances of using scCO2 or/and ILs as amphiphile self-assembly media in the last decade. The amphiphile self-assemblies in scCO2 and ILs are first reviewed, followed by the discussion on combination of scCO2 and ILs in creating microemulsions or emulsions. Some future directions on the amphiphile self-assemblies in scCO2 and ILs are highlighted. PMID:25000970

  6. 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

  7. 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...

  8. Antifungal Activity of 14-Helical β-Peptides against Planktonic Cells and Biofilms of Candida Species

    Directory of Open Access Journals (Sweden)

    Namrata Raman

    2015-08-01

    Full Text Available Candida albicans is the most prevalent cause of fungal infections and treatment is further complicated by the formation of drug resistant biofilms, often on the surfaces of implanted medical devices. In recent years, the incidence of fungal infections by other pathogenic Candida species such as C. glabrata, C. parapsilosis and C. tropicalis has increased. Amphiphilic, helical β-peptide structural mimetics of natural antimicrobial α-peptides have been shown to exhibit specific planktonic antifungal and anti-biofilm formation activity against C. albicans in vitro. Here, we demonstrate that β-peptides are also active against clinically isolated and drug resistant strains of C. albicans and against other opportunistic Candida spp. Different Candida species were susceptible to β-peptides to varying degrees, with C. tropicalis being the most and C. glabrata being the least susceptible. β-peptide hydrophobicity directly correlated with antifungal activity against all the Candida clinical strains and species tested. While β-peptides were largely ineffective at disrupting existing Candida biofilms, hydrophobic β-peptides were able to prevent the formation of C. albicans, C. glabrata, C. parapsilosis and C. tropicalis biofilms. The broad-spectrum antifungal activity of β-peptides against planktonic cells and in preventing biofilm formation suggests the promise of this class of molecules as therapeutics.

  9. Antifungal Activity of 14-Helical β-Peptides against Planktonic Cells and Biofilms of Candida Species.

    Science.gov (United States)

    Raman, Namrata; Lee, Myung-Ryul; Lynn, David M; Palecek, Sean P

    2015-01-01

    Candida albicans is the most prevalent cause of fungal infections and treatment is further complicated by the formation of drug resistant biofilms, often on the surfaces of implanted medical devices. In recent years, the incidence of fungal infections by other pathogenic Candida species such as C. glabrata, C. parapsilosis and C. tropicalis has increased. Amphiphilic, helical β-peptide structural mimetics of natural antimicrobial α-peptides have been shown to exhibit specific planktonic antifungal and anti-biofilm formation activity against C. albicans in vitro. Here, we demonstrate that β-peptides are also active against clinically isolated and drug resistant strains of C. albicans and against other opportunistic Candida spp. Different Candida species were susceptible to β-peptides to varying degrees, with C. tropicalis being the most and C. glabrata being the least susceptible. β-peptide hydrophobicity directly correlated with antifungal activity against all the Candida clinical strains and species tested. While β-peptides were largely ineffective at disrupting existing Candida biofilms, hydrophobic β-peptides were able to prevent the formation of C. albicans, C. glabrata, C. parapsilosis and C. tropicalis biofilms. The broad-spectrum antifungal activity of β-peptides against planktonic cells and in preventing biofilm formation suggests the promise of this class of molecules as therapeutics. PMID:26287212

  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. PMID:25929870

  11. Engineered Adhesion Peptides for Improved Silicon Adsorption.

    Science.gov (United States)

    Ramakrishnan, Sathish Kumar; Jebors, Said; Martin, Marta; Cloitre, Thierry; Agarwal, Vivechana; Mehdi, Ahmad; Martinez, Jean; Subra, Gilles; Gergely, Csilla

    2015-11-01

    Engineering peptides that present selective recognition and high affinity for a material is a major challenge for assembly-driven elaboration of complex systems with wide applications in the field of biomaterials, hard-tissue regeneration, and functional materials for therapeutics. Peptide-material interactions are of vital importance in natural processes but less exploited for the design of novel systems for practical applications because of our poor understanding of mechanisms underlying these interactions. Here, we present an approach based on the synthesis of several truncated peptides issued from a silicon-specific peptide recovered via phage display technology. We use the photonic response provided by porous silicon microcavities to evaluate the binding efficiency of 14 different peptide derivatives. We identify and engineer a short peptide sequence (SLVSHMQT), revealing the highest affinity for p(+)-Si. The molecular recognition behavior of the obtained peptide fragment can be revealed through mutations allowing identification of the preferential affinity of certain amino acids toward silicon. These results constitute an advance in both the engineering of peptides that reveal recognition properties for silicon and the understanding of biomolecule-material interactions.

  12. Synthesis of antibacterial amphiphilic elastomer based on polystyrene-block-polyisoprene-block-polystyrene via thiol-ene addition

    Energy Technology Data Exchange (ETDEWEB)

    Keleş, Elif, E-mail: elifkelesh@hotmail.com [Department of Chemistry, Bülent Ecevit University, Zonguldak 67100 (Turkey); Hazer, Baki, E-mail: bhazer2@yahoo.com [Department of Chemistry, Bülent Ecevit University, Zonguldak 67100 (Turkey); Cömert, Füsun B. [Department of Microbiology, Faculty of Medicine, Bülent Ecevit University, 67600 Zonguldak (Turkey)

    2013-04-01

    A new type of amphiphilic antibacterial elastomer has been described. Thermoplastic elastomer, polystyrene–block-polyisoprene–block-polystyrene (PS–b-PI–b-PS) triblock copolymer was functionalized in toluene solution by free radical mercaptan addition in order to obtain an amphiphilic antibacterial elastomer. Thiol terminated PEG was grafted through the double bonds of PS–b-PI–b-PS via free radical thiol-ene coupling reaction. The antibacterial properties of the amphiphilic graft copolymers were observed. The original and the modified polymers were used to create microfibers in an electro-spinning process. Topology of the electrospun micro/nanofibers were studied by using scanning electron microscopy (SEM). The chemical structures of the amphiphilic comb type graft copolymers were elucidated by the combination of elemental analysis, {sup 1}H NMR, {sup 13}C NMR, GPC and FTIR. - Graphical abstract: Double bonds of polyisoprene units in polystyrene–block-polyisoprene–block-polystyrene triblock copolymer were partially capped with PEG containing mercapto end group via thiol-ene addition in order to obtain antibacterial amphiphilic elastomer. Nano fibers from amphiphilic graft polymers solution were produced by electrospinning. The PEG grafted copolymer inhibits very effectively bacterial growth. Highlights: ► A commercial synthetic elastomer was grafted with PEG to obtain amphiphilic elastomer. ► Amphiphilic elastomer shows antibacterial properties. ► Electrospun micro fibers of the amphiphilic elastomer tend to globular formation.

  13. 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.

  14. Synthesis, Characterization, and Evaluation of a Novel Amphiphilic Polymer RGD-PEG-Chol for Target Drug Delivery System

    Directory of Open Access Journals (Sweden)

    Shi Zeng

    2014-01-01

    Full Text Available An amphiphilic polymer RGD-PEG-Chol which can be produced in large scale at a very low cost has been synthesized successfully. The synthesized intermediates and final products were characterized and confirmed by 1H nuclear magnetic resonance spectrum (1H NMR and Fourier transform infrared spectrum (FT-IR. The paclitaxel- (PTX- loaded liposomes based on RGD-PEG-Chol were then prepared by film formation method. The liposomes had a size within 100 nm and significantly enhanced the cytotoxicity of paclitaxel to B16F10 cell as demonstrated by MTT test (IC50 = 0.079 μg/mL of RGD-modified PTX-loaded liposomes compared to 9.57 μg/mL of free PTX. Flow cytometry analysis revealed that the cellular uptake of coumarin encapsulated in the RGD-PEG-Chol modified liposome was increased for HUVEC cells. This work provides a reasonable, facile, and economic approach to prepare peptide-modified liposome materials with controllable performances and the obtained linear RGD-modified PTX-loaded liposomes might be attractive as a drug delivery system.

  15. Peptides Regulate Cortical Thymocytes Differentiation, Proliferation, and Apoptosis

    Directory of Open Access Journals (Sweden)

    V. Kh. Khavinson

    2011-01-01

    Full Text Available The processes of differentiation, proliferation, and apoptosis were studied in a cell culture of human cortical thymocytes under the influence of short peptides T-32 (Glu-Asp-Ala and T-38 (Lys-Glu-Asp. Peptides T-32 and T-38 amplified cortical thymocytes differentiation towards regulatory T cells, increased their proliferative activity, and decreased the level of apoptosis. Moreover, peptides under study stimulated proliferative and antiapoptotic activity of the mature regulatory T cells.

  16. Two-dimensional Effects of Hydrogel Self-organized from IKVAV-containing Peptides on Growth and Differentiation of NSCs

    Institute of Scientific and Technical Information of China (English)

    SONG Yulin; ZHENG Qixin; WU Yongchao; GUO Xiaodong

    2009-01-01

    The neural stem cells (NSCs) were seeded in the surf ace layer of hydrogels made of IKVAV-containing peptide amphiphile. Two-dimensional effects of hydrogel on growth and differ-entiation of NSCs were investigated. Peptide was synthesized in solid way. Cells were harvested from the cerebral cortex of neonatal mice, identified by immunohisto chemical methods. Cells were incu-bated in the surface layer of self-assembled peptide hydrogel and coverslips for seven days respec-tively,detected immunocy to chemically for NF and GFAP. The molecular weight (MW) of Peptide was1438 and purity was 95.22%. Cells were identified as Nestin-positive NSCs. TEM showed that hy-drogel was composed of interactive nanofibers. NSCs extended processes, and were able to be dif-ferentiated into NF-positive neurons with red fluorescence and GFAP-positive astrocytes with greenone in the surface of hydrogel. However, NSCs only formed undifferentiated neurospheres in thesurface layer of coverslips. Results indicate that the self-assembled hydrogel from peptide amphiphile has good cyto-compatibility to NSCs and induced their differentiation.

  17. 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

    2013-01-01

    Polymeric films with nanoscale networks were prepared by selectively swelling an amphiphilic diblock copolymer, polystyrene-block-poly(4-vinylpyridine) (PS-b-P4VP), with the CO2-expanded liquid (CXL), CO2-methanol. The phase behavior of the CO2-methanol system was investigated by both theoretical calculation and experiments, revealing that methanol can be expanded by CO2, forming homogeneous CXL under the experimental conditions. When treated with the CO2-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.Polymeric films with nanoscale networks were prepared by selectively swelling an amphiphilic diblock copolymer, polystyrene-block-poly(4-vinylpyridine) (PS-b-P4VP), with the CO2-expanded liquid (CXL), CO2-methanol. The phase behavior of the CO2-methanol system was investigated by both theoretical calculation and experiments, revealing that methanol can be expanded by CO2, forming homogeneous CXL under the experimental conditions. When treated with the CO2-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

  18. Perfluorocyclobutyl-containing Amphiphilic Block Copolymers Synthesized by RAFT Polymerization

    Institute of Scientific and Technical Information of China (English)

    LI, Yongjun; ZHANG, Sen; FENG, Chun; ZHANG, Yaqin; LI, Qingnuan; LI, Wenxin; HUANG, Xiaoyu

    2009-01-01

    Amphiphilic block copolymers containing hydrophobic perfluorocyclobutyl-based (PFCB) polyacrylate and hydrophilic poly(ethylene glycol) (PEG) segments were prepared via reversible addition-fragmentation chain transfer (RAP-T) polymerization. The PFCB-containing acrylate monomer, p-(2-(p-tolyloxy)perfluorocyclobutoxy)phenyl acrylate, was first synthesized from commercially available compounds in good yields, and this kind of acrylate monomer can be homopolymerized by free radical polymerization or RAFT polymerization. Kinetic study showed the 2,2'-azobis(isobutyronitrile) (AIBN) initiated and cumyl dithiobenzoate (CDB) mediated RAFT polymerization was in a living fashion, as suggested by the fact that the number-average molecular weights (M_n) increased linearly with the conversions of the monomer, while the polydispersity indices kept less than 1.10. The block polymers with narrow molecular weight distributions (M_w/M_n≤1.21) were prepared through RAFT polymerization using PEG monomethyl ether capped with 4-cyanopentanoic acid dithiobenzoate end group as the macro chain transfer agent (mPEG-CTA). The length of the hydrophobic segment can be tuned by the feed ratio of the PFCB-based acrylate monomer and the extending of the polymerization time. The micellization behavior of the block copolymers in aqueous media was investigated by the fluorescence probe technique.

  19. Photochemical Isomerization and Topochemical Polymerization of the Programmed Asymmetric Amphiphiles

    Science.gov (United States)

    Kim, Dae-Yoon; Lee, Sang-A.; Jung, Daseal; Jeong, Kwang-Un

    2016-06-01

    For the advancement in multi-stimuli responsive optical devices, we report the elaborate molecular engineering of the dual photo-functionalized amphiphile (abbreviated as AZ1DA) containing both a photo-isomerizable azobenzene and a photo-polymerizable diacetylene. To achieve the efficient photochemical reactions in thin solid films, the self-assembly of AZ1DA molecules into the ordered phases should be precisely controlled and efficiently utilized. First, the remote-controllable light shutter is successfully demonstrated based on the reversible trans-cis photo-isomerization of azobenzene group in the smectic A mesophase. Second, the self-organized monoclinic crystal phase allows us to validate the photo-polymerization of diacetylene moiety for the photo-patterned thin films and the thermo-responsible color switches. From the demonstrations of optically tunable thin films, it is realized that the construction of strong relationships between chemical structures, molecular packing structures and physical properties of the programmed molecules is the core research for the development of smart and multifunctional soft materials.

  20. Synthesis, aggregation, and chiroptical properties of chiral, amphiphilic dendrimers.

    Science.gov (United States)

    Laufersweiler, M J; Rohde, J M; Chaumette, J L; Sarazin, D; Parquette, J R

    2001-09-21

    The syntheses of amphiphilic dendrimers based on 3,5-dihydroxybenzyl alcohol containing tri- or tetrafunctional chiral central cores and allyl ester termini are described. Water solubility is imparted to the dendrimers via a palladium-catalyzed deprotection of the peripheral allyl esters. This method affords complete deprotection of the carboxylate surface because, in contrast to the basic hydrolysis of methyl ester termini, the solubility of partially hydrolyzed intermediates is maintained throughout the course of the deprotection, thereby avoiding precipitation during the reaction. Chiroptical analysis indicates that the structure of the dendrimers collapses in water, resulting in an increased steric effect upon the central core that is manifested by lower optical rotatory power. However, contributions to the chiroptical properties from the dendron branch segments were not evident in water or organic media, suggesting that chiral substructures were not developing in the branch segments of the dendrimers. Multiangle light scattering studies revealed that the dendrimers experienced significant aggregation in aqueous media that decreased at higher generations. This behavior could be rationalized by a change in conformational preference from a disklike conformation at low generations to a more globular conformation at higher generations. PMID:11559197

  1. Amphiphilic self-assembly of alkanols in protic ionic liquids.

    Science.gov (United States)

    Jiang, Haihui Joy; FitzGerald, Paul A; Dolan, Andrew; Atkin, Rob; Warr, Gregory G

    2014-08-21

    Strong cohesive forces in protic ionic liquids (PILs) can induce a liquid nanostructure consisting of segregated polar and apolar domains. Small-angle X-ray scattering has shown that these forces can also induce medium chain length n-alkanols to self-assemble into micelle- and microemulsion-like structures in ethylammonium (EA(+)) and propylammonium (PA(+)) PILs, in contrast to their immiscibility with both water and ethanolammonium (EtA(+)) PILs. These binary mixtures are structured on two distinct length scales: one associated with the self-assembled n-alkanol aggregates and the other with the underlying liquid nanostructure. This suggests that EA(+) and PA(+) enable n-alkanol aggregation by acting as cosurfactants, which EtA(+) cannot do because its terminating hydroxyl renders the cation nonamphiphilic. The primary determining factor for miscibility and self-assembly is the ratio of alkyl chain lengths of the alkanol and PIL cation, modulated by the anion type. These results show how ILs can support the self-assembly of nontraditional amphiphiles and enable the creation of new forms of soft matter. PMID:25068766

  2. Optimization of hypocrellin B derivative amphiphilicity and biological activity

    Institute of Scientific and Technical Information of China (English)

    LIU Xin; XIE Jie; ZHANG LuYong; CHEN HongXia; GU Ying; ZHAO JingQuan

    2009-01-01

    To satisfy the dual requirements of the fluent transportation in blood and the affinity to the target tissues of vascular diseases, hypocrellin derivatives with optimized amphiphilicity are expected. In this work, 3-amino-1-propanesulfonic acid and 4-amino-1-butanesulfonic acid substituted hypocrellin B,named compounds 1 and 2, were designed, synthesized in high yields and characterized. Besides greatly strengthened red absorption, the maximum solubility of compound 2 in phosphate buffered saline (PBS) is 4.2 mg/mL which is just enough to prepare an aqueous solution for intravenous injection in clinically acceptable concentration, while the partition coefficient between n-octanol and PBS,5.6, benefits the cell-uptake and biological activity as well. Furthermore, EPR measurements reveal that the photosensitization activities of the two compounds to generate semiquinone anion radicals, superoxide anion radicals and singlet oxygen are a little bit higher than those of taurine substituted hypocrellin B (THB), but the photodynamic activities to human lung cancer A549 cells are several times that of THB, mainly due to increases in lipophilicity and cell-uptake.

  3. Synthesis and Bioactivities of Kanamycin B-Derived Cationic Amphiphiles.

    Science.gov (United States)

    Fosso, Marina Y; Shrestha, Sanjib K; Green, Keith D; Garneau-Tsodikova, Sylvie

    2015-12-10

    Cationic amphiphiles derived from aminoglycosides (AGs) have been shown to exhibit enhanced antimicrobial activity. Through the attachment of hydrophobic residues such as linear alkyl chains on the AG backbone, interesting antibacterial and antifungal agents with a novel mechanism of action have been developed. Herein, we report the design and synthesis of seven kanamycin B (KANB) derivatives. Their antibacterial and antifungal activities, along with resistance/enzymatic, hemolytic, and cytotoxicity assays were also studied. Two of these compounds, with a C12 and C14 aliphatic chain attached at the 6″-position of KANB through a thioether linkage, exhibited good antibacterial and antifungal activity, were poorer substrates than KANB for several AG-modifying enzymes, and could delay the development of resistance in bacteria and fungi. Also, they were both relatively less hemolytic than the known membrane targeting antibiotic gramicidin and the known antifungal agent amphotericin B and were not toxic at their antifungal MIC values. Their oxidation to sulfones was also demonstrated to have no effect on their activities. Moreover, they both acted synergistically with posaconazole, an azole currently used in the treatment of human fungal infections. PMID:26592740

  4. 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 pro...

  5. Self-assembly of ssDNA-amphiphiles into micelles, nanotapes and nanotubes

    Science.gov (United States)

    Pearce, Timothy R.

    The field of DNA nanotechnology utilizes DNA as a construction material to create functional supramolecular and multi-dimensional structures like two-dimensional periodic lattices and three-dimensional polyhedrons with order on the nanometer scale for many nanotechnology applications including molecular templating, nanosensors, and drug delivery. Single-stranded DNA (ssDNA) is often used to create these nanostructures as the DNA bases provide an intrinsic molecular code that can be exploited to allow for the programmed assembly of structures based upon Watson-Crick base-pairing. However, engineering these complex structures from biopolymers alone requires careful design to ensure that the intrinsic forces responsible for organizing the materials can produce the desired structures. Additional control over supramolecular assembly can be achieved by chemically modifying the ssDNA with hydrophobic moieties to create amphiphilic molecules, which adds the hydrophobic interaction to the list of contributing forces that drive the self-assembly process. We first explored the self-assembly behavior of a set of ssDNA aptamer-amphiphiles composed of the same hydrophobic tail and hydrophilic ssDNA aptamer headgroup but with different spacer molecules linking these groups together. Through the use of cryo-transmission electron microscopy (cryo-TEM), small angle x-ray scattering (SAXS), and circular dichroism (CD) we show that the aptamer-amphiphiles can assemble into a variety of structures depending on the spacer used. We demonstrated, for the first time, the creation of self-assembled aptamer-amphiphile nanotape structures and show that the choice of the spacer used in the design of aptamer-amphiphiles can influence their supramolecular self-assembly as well as the secondary structure of the aptamer headgroup. We next explored the role of the ssDNA headgroup on the amphiphile self-assembly behavior by designing amphiphiles with headgroups of multiple lengths and nucleotides

  6. New cationic amphiphilic compounds as potential antibacterial agents

    NARCIS (Netherlands)

    Visser, Peter Christian de

    2006-01-01

    Het onderwerp van het in dit proefschrift beschreven onderzoek is de ontwikkeling van nieuwe verbindingen met antibacteriële activiteit gericht tegen Gram-negatieve bacteriën. Deze verbindingen zijn afgeleid van kationische antimicrobiële peptides (CAPs), een klasse van antibiotica die volgens ander

  7. Towards the improved discovery and design of functional peptides: common features of diverse classes permit generalized prediction of bioactivity.

    Directory of Open Access Journals (Sweden)

    Catherine Mooney

    Full Text Available The conventional wisdom is that certain classes of bioactive peptides have specific structural features that endow their particular functions. Accordingly, predictions of bioactivity have focused on particular subgroups, such as antimicrobial peptides. We hypothesized that bioactive peptides may share more general features, and assessed this by contrasting the predictive power of existing antimicrobial predictors as well as a novel general predictor, PeptideRanker, across different classes of peptides.We observed that existing antimicrobial predictors had reasonable predictive power to identify peptides of certain other classes i.e. toxin and venom peptides. We trained two general predictors of peptide bioactivity, one focused on short peptides (4-20 amino acids and one focused on long peptides (> 20 amino acids. These general predictors had performance that was typically as good as, or better than, that of specific predictors. We noted some striking differences in the features of short peptide and long peptide predictions, in particular, high scoring short peptides favour phenylalanine. This is consistent with the hypothesis that short and long peptides have different functional constraints, perhaps reflecting the difficulty for typical short peptides in supporting independent tertiary structure.We conclude that there are general shared features of bioactive peptides across different functional classes, indicating that computational prediction may accelerate the discovery of novel bioactive peptides and aid in the improved design of existing peptides, across many functional classes. An implementation of the predictive method, PeptideRanker, may be used to identify among a set of peptides those that may be more likely to be bioactive.

  8. Cationic Amphiphiles Increase Activity of Aminoglycoside Antibiotic Tobramycin in the Presence of Airway Polyelectrolytes

    Energy Technology Data Exchange (ETDEWEB)

    Purdy Drew, Kirstin R.; Sanders, Lori K.; Culumber, Zachary W.; Zribi, Olena; Wong, Gerard C.L.; (UIUC)

    2009-06-17

    It is empirically known that anionic polyelectrolytes present in cystic fibrosis (CF) airways due to bacterial infection significantly decrease the activity of cationic antimicrobials via electrostatic binding. In this work, we use synchrotron small-angle X-ray scattering to investigate the interaction between tobramycin, an aminoglycoside antibiotic commonly administered to CF patients via inhalation, with DNA, which is found in high concentrations in the CF airway. We find that interactions between DNA and tobramycin are significantly modified by the presence of mixtures of amphiphilic molecules. We measure a hierarchy of self-assembled structures formed between tobramycin, DNA, and the amphiphile mixtures and show how interactions between these components can be controlled. Results indicate that mixtures of cationic and negative curvature amphiphiles optimized for DNA binding via charge matching and curvature matching can competitively displace bound tobramycin from DNA and thereby drastically suppress tobramycin-DNA binding and resultant antimicrobial inactivation. Growth inhibition assays confirm the increased activity of tobramycin in the presence of DNA with the addition of the amphiphiles. These results suggest that optimized cationic amphiphile solutions have the potential to enhance antimicrobial function in highly infected environments that contain increased concentrations of anionic inflammatory polymers.

  9. Cationic Amphiphiles Increase Activity of Aminoglycoside Antibiotic Tobramycin in the Presence of Airway Polyelectrolytes

    Energy Technology Data Exchange (ETDEWEB)

    Drew, K.R.Purdy; Sanders, L.K.; Culumber, Z.W.; Zribi, O.; Wong, G.C.L.

    2009-05-21

    It is empirically known that anionic polyelectrolytes present in cystic fibrosis (CF) airways due to bacterial infection significantly decrease the activity of cationic antimicrobials via electrostatic binding. In this work, we use synchrotron small-angle X-ray scattering to investigate the interaction between tobramycin, an aminoglycoside antibiotic commonly administered to CF patients via inhalation, with DNA, which is found in high concentrations in the CF airway. We find that interactions between DNA and tobramycin are significantly modified by the presence of mixtures of amphiphilic molecules. We measure a hierarchy of self-assembled structures formed between tobramycin, DNA, and the amphiphile mixtures and show how interactions between these components can be controlled. Results indicate that mixtures of cationic and negative curvature amphiphiles optimized for DNA binding via charge matching and curvature matching can competitively displace bound tobramycin from DNA and thereby drastically suppress tobramycin-DNA binding and resultant antimicrobial inactivation. Growth inhibition assays confirm the increased activity of tobramycin in the presence of DNA with the addition of the amphiphiles. These results suggest that optimized cationic amphiphile solutions have the potential to enhance antimicrobial function in highly infected environments that contain increased concentrations of anionic inflammatory polymers.

  10. Cholesterol-Targeted Anticancer and Apoptotic Effects of Anionic and Polycationic Amphiphilic Cyclodextrin Nanoparticles.

    Science.gov (United States)

    Varan, Gamze; Öncül, Selin; Ercan, Ayşe; Benito, Juan M; Ortiz Mellet, Carmen; Bilensoy, Erem

    2016-10-01

    Amphiphilic cyclodextrins (CDs) are biocompatible derivatives of natural CDs and are able to form nanoparticles or polyplexes spontaneously. In this study, nanoparticles prepared from nonionic (6OCaproβCD) or cationic amphiphilic CD (PC βCDC6) were used comparatively to develop nanoparticles intended for breast cancer therapy. The characterization of these nanoparticles was performed both by in vitro and cell culture studies. Furthermore, the apoptotic and cytotoxic effects of blank amphiphilic CDs were demonstrated by various mechanistic methods including Caspase-8 activity, lipid peroxidation assay, TUNEL assay, Tali(®)-based image analysis, cholesterol assay, and gene expression studies. Blank nanoparticles exerted cytotoxicity against a variety of cancer cells (MCF-7, HeLa, HepG2, and MB49) but none to healthy cells (L929, G/G). Interestingly, blank 6OCaproβCD and blank PC βCDC6 derivatives were found to be intrinsically effective on cell number and membrane integrity of MCF-7 cells in apoptosis studies. Further in-depth studies were performed to elucidate the selective mechanism of anticancer action in MCF-7 cells caused by these amphiphilic CDs. In conclusion, blank amphiphilic CD nanoparticles induced apoptosis through mitochondrial pathway targeted to cholesterol microdomains in cancer cell membrane. PMID:27488900

  11. Cationic Amphiphiles Increase Activity of Aminoglycoside Antibiotic Tobramycin in the Presence of Airway Polyelectrolytes

    International Nuclear Information System (INIS)

    It is empirically known that anionic polyelectrolytes present in cystic fibrosis (CF) airways due to bacterial infection significantly decrease the activity of cationic antimicrobials via electrostatic binding. In this work, we use synchrotron small-angle X-ray scattering to investigate the interaction between tobramycin, an aminoglycoside antibiotic commonly administered to CF patients via inhalation, with DNA, which is found in high concentrations in the CF airway. We find that interactions between DNA and tobramycin are significantly modified by the presence of mixtures of amphiphilic molecules. We measure a hierarchy of self-assembled structures formed between tobramycin, DNA, and the amphiphile mixtures and show how interactions between these components can be controlled. Results indicate that mixtures of cationic and negative curvature amphiphiles optimized for DNA binding via charge matching and curvature matching can competitively displace bound tobramycin from DNA and thereby drastically suppress tobramycin-DNA binding and resultant antimicrobial inactivation. Growth inhibition assays confirm the increased activity of tobramycin in the presence of DNA with the addition of the amphiphiles. These results suggest that optimized cationic amphiphile solutions have the potential to enhance antimicrobial function in highly infected environments that contain increased concentrations of anionic inflammatory polymers

  12. Fluorinated amphiphiles control the insertion of α-hemolysin pores into lipid bilayers.

    Science.gov (United States)

    Raychaudhuri, Pinky; Li, Qiuhong; Mason, Amy; Mikhailova, Ellina; Heron, Andrew J; Bayley, Hagan

    2011-03-15

    The insertion of fully folded and assembled ion channels and pores into planar lipid bilayers for electrical recording has been facilitated by the use of conventional detergents at a final concentration below the critical micelle concentration (CMC). After the desired number of channels or pores (often one) has been incorporated into a bilayer, it is important to prevent further insertion events, which is often done by awkward techniques such as perfusion. Here, we show that the addition of single-chain fluorinated amphiphiles (F-amphiphiles) with zwitterionic, simple neutral, and neutral oligomeric headgroups at a concentration above the CMC prevents the further insertion of staphylococcal α-hemolysin pores, MspA pores, and Kcv potassium channels into lipid bilayers. We found the commercially available F(6)FC (fluorinated fos-choline with a C(6)F(13)C(2)H(4) chain) to be the least perturbing and most effective agent for this purpose. Bilayers are known to be resistant to F-amphiphiles, which in this case we suppose sequester the pores and channels within amphiphile aggregates. We suggest that F-amphiphiles might be useful in the fabrication of bilayer arrays for nanopore sensor devices and the rapid screening of membrane proteins. PMID:21275394

  13. Creating functional peptide architectures at interfaces

    Science.gov (United States)

    Tirrell, Matthew

    2001-03-01

    Short peptide sequences, derived from whole proteins, can be useful synthetic agents for conferring a specific biological function to a material surface. Their ability to do this depends on delivering them to the surface in a biologically recognizable form, that is in a spatial configuration that is not too different from that adopted by the peptide in the whole protein. Most functional proteins have secondary and tertiary levels of structure that are essential to their activities; peptides have simpler but no less important structures. In our work, we have focussed on peptides derived from extracellular matrix proteins. We have found that attaching synthetic lipid tails to peptides fragments gives them two very useful properties for surface modification. The hydrophobic tails give rise to a self-assembly capacity enabling these molecules to organize into membrane, monolayer and bilayer structures. Less expected is that this level of self-assembly induces a second level in the peptide headgroup. Peptides from alpha-helical and triple-helical regions of protein are induced by the lipid tails to form protein-like secondary structures and therefore to have more effective biological activity.

  14. 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...

  15. Aggregation behaviour of amphiphilic cyclodextrins: the nucleation stage by atomistic molecular dynamics simulations

    Directory of Open Access Journals (Sweden)

    Giuseppina Raffaini

    2015-12-01

    Full Text Available Amphiphilically modified cyclodextrins may form various supramolecular aggregates. Here we report a theoretical study of the aggregation of a few amphiphilic cyclodextrins carrying hydrophobic thioalkyl groups and hydrophilic ethylene glycol moieties at opposite rims, focusing on the initial nucleation stage in an apolar solvent and in water. The study is based on atomistic molecular dynamics methods with a “bottom up” approach that can provide important information about the initial aggregates of few molecules. The focus is on the interaction pattern of amphiphilic cyclodextrin (aCD, which may interact by mutual inclusion of the substituent groups in the hydrophobic cavity of neighbouring molecules or by dispersion interactions at their lateral surface. We suggest that these aggregates can also form the nucleation stage of larger systems as well as the building blocks of micelles, vesicle, membranes, or generally nanoparticles thus opening new perspectives in the design of aggregates correlating their structures with the pharmaceutical properties.

  16. Aggregation behaviour of amphiphilic cyclodextrins: the nucleation stage by atomistic molecular dynamics simulations.

    Science.gov (United States)

    Raffaini, Giuseppina; Mazzaglia, Antonino; Ganazzoli, Fabio

    2015-01-01

    Amphiphilically modified cyclodextrins may form various supramolecular aggregates. Here we report a theoretical study of the aggregation of a few amphiphilic cyclodextrins carrying hydrophobic thioalkyl groups and hydrophilic ethylene glycol moieties at opposite rims, focusing on the initial nucleation stage in an apolar solvent and in water. The study is based on atomistic molecular dynamics methods with a "bottom up" approach that can provide important information about the initial aggregates of few molecules. The focus is on the interaction pattern of amphiphilic cyclodextrin (aCD), which may interact by mutual inclusion of the substituent groups in the hydrophobic cavity of neighbouring molecules or by dispersion interactions at their lateral surface. We suggest that these aggregates can also form the nucleation stage of larger systems as well as the building blocks of micelles, vesicle, membranes, or generally nanoparticles thus opening new perspectives in the design of aggregates correlating their structures with the pharmaceutical properties. PMID:26734094

  17. Synthesis of Dumbbell-shaped Hyperbranched Amphiphilic Block Copolymer by Controlled Atom Transfer Radical Polymerization

    Energy Technology Data Exchange (ETDEWEB)

    Kim, In Kyoung; An, Sung Guk; Cho, Chang Gi [Center for Advanced Functional Polymers, Department of Fiber and Polymer Science, Hanyang University, Seoul (Korea); Noh, Si Tae [Department of Chemical Engineering, Hanyang University, Ansan (Korea)

    2001-04-01

    Amphiphilic block copolymers containing hydrophilic ethylene glycol core and hyperbranched polystyrene (PS) arm were synthesized by atom transfer radical polymerization using hydrophilic macroinitiator and p-chloromethyl styrene (CMS) as AB type monomer. Hydrophilic poly(ethylene glycol)(PEG) macroinitiators with difuntional groups were synthesized by reacting PEG and 2-bromopropionyl bromide. The chemical structure, molecular weight, and polydispersity index of the amphiphilic block copolymer were characterized by {sup 1}H-NMR spectroscopy and GPC analysis. The molecular weight increased as the reaction time increased. Polydispersity index of the obtained polymer was relatively narrow (below 1.39). To control chain density of the hyperbranched PS, styrene and CMS were copolymerized. It was found that amphiphilic block copolymer molecule underwent conformational change in different solvents based on the result for {sup 1}H-NMR spectroscopic analysis. 29 refs., 8 figs., 2 tabs.

  18. Aggregation behaviour of amphiphilic cyclodextrins: the nucleation stage by atomistic molecular dynamics simulations

    Science.gov (United States)

    Mazzaglia, Antonino; Ganazzoli, Fabio

    2015-01-01

    Summary Amphiphilically modified cyclodextrins may form various supramolecular aggregates. Here we report a theoretical study of the aggregation of a few amphiphilic cyclodextrins carrying hydrophobic thioalkyl groups and hydrophilic ethylene glycol moieties at opposite rims, focusing on the initial nucleation stage in an apolar solvent and in water. The study is based on atomistic molecular dynamics methods with a “bottom up” approach that can provide important information about the initial aggregates of few molecules. The focus is on the interaction pattern of amphiphilic cyclodextrin (aCD), which may interact by mutual inclusion of the substituent groups in the hydrophobic cavity of neighbouring molecules or by dispersion interactions at their lateral surface. We suggest that these aggregates can also form the nucleation stage of larger systems as well as the building blocks of micelles, vesicle, membranes, or generally nanoparticles thus opening new perspectives in the design of aggregates correlating their structures with the pharmaceutical properties. PMID:26734094

  19. 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.

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

    Science.gov (United States)

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

    2014-08-01

    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.

  1. Construction of Epidermal Growth Factor Receptor Peptide Magnetic Nanovesicles with Lipid Bilayers for Enhanced Capture of Liver Cancer Circulating Tumor Cells.

    Science.gov (United States)

    Ding, Jian; Wang, Kai; Tang, Wen-Jie; Li, Dan; Wei, You-Zhen; Lu, Ying; Li, Zong-Hai; Liang, Xiao-Fei

    2016-09-20

    Highly effective targeted tumor recognition via vectors is crucial for cancer detection. In contrast to antibodies and proteins, peptides are direct targeting ligands with a low molecular weight. In the present study, a peptide magnetic nanovector platform containing a lipid bilayer was designed using a peptide amphiphile (PA) as a skeleton material in a controlled manner without surface modification. Fluorescein isothiocyanate-labeled epidermal growth factor receptor (EGFR) peptide nanoparticles (NPs) could specifically bind to EGFR-positive liver tumor cells. EGFR peptide magnetic vesicles (EPMVs) could efficiently recognize and separate hepatoma carcinoma cells from cell solutions and treated blood samples (ratio of magnetic EPMVs versus anti-EpCAM NPs: 3.5 ± 0.29). Analysis of the circulating tumor cell (CTC) count in blood samples from 32 patients with liver cancer showed that EPMVs could be effectively applied for CTC capture. Thus, this nanoscale, targeted cargo-packaging technology may be useful for designing cancer diagnostic systems.

  2. 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.

  3. 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.

  4. 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....

  5. 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....

  6. 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....

  7. 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....

  8. 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....

  9. Sacrificial amphiphiles: Eco-friendly chemical herders as oil spill mitigation chemicals.

    Science.gov (United States)

    Gupta, Deeksha; Sarker, Bivas; Thadikaran, Keith; John, Vijay; Maldarelli, Charles; John, George

    2015-06-01

    Crude oil spills are a major threat to marine biota and the environment. When light crude oil spills on water, it forms a thin layer that is difficult to clean by any methods of oil spill response. Under these circumstances, a special type of amphiphile termed as "chemical herder" is sprayed onto the water surrounding the spilled oil. The amphiphile forms a monomolecular layer on the water surface, reducing the air-sea surface tension and causing the oil slick to retract into a thick mass that can be burnt in situ. The current best-known chemical herders are chemically stable and nonbiodegradable, and hence remain in the marine ecosystem for years. We architect an eco-friendly, sacrificial, and effective green herder derived from the plant-based small-molecule phytol, which is abundant in the marine environment, as an alternative to the current chemical herders. Phytol consists of a regularly branched chain of isoprene units that form the hydrophobe of the amphiphile; the chain is esterified to cationic groups to form the polar group. The ester linkage is proximal to an allyl bond in phytol, which facilitates the hydrolysis of the amphiphile after adsorption to the sea surface into the phytol hydrophobic tail, which along with the unhydrolyzed herder, remains on the surface to maintain herding action, and the cationic group, which dissolves into the water column. Eventual degradation of the phytol tail and dilution of the cation make these sacrificial amphiphiles eco-friendly. The herding behavior of phytol-based amphiphiles is evaluated as a function of time, temperature, and water salinity to examine their versatility under different conditions, ranging from ice-cold water to hot water. The green chemical herder retracted oil slicks by up to ~500, 700, and 2500% at 5°, 20°, and 35°C, respectively, during the first 10 min of the experiment, which is on a par with the current best chemical herders in practice. PMID:26601197

  10. Fusiogenic activity of natural amphiphiles, 5-n-alkylresorcinols in a yeast protoplast system.

    Science.gov (United States)

    Kozubek, A; Skała, J

    1995-01-01

    Two homologues of cereal grain resorcinolic lipids, 5-n-heptadecylresorcinol and 5-n-heptadecenylresorcinol studied in the system employing yeast cell protoplasts showed marked fusiogenic activity. The frequency of hybrid formation induced by studied amphiphiles was significantly higher than that obtained with the use of 40% (w/v) polyethylene glycol 4000. The resorcinolic lipids as fusion-inducing agents did not affect regeneration of the cellular wall. The fusiogenic activity of resorcinolic lipids lost when calcium ions were absent in the medium. Fusiogenic activity of studied amphiphiles is related to their ability to induce non-bilayer structures within the cellular membranes. PMID:8579682

  11. Monte Carlo simulation for the micellar behavior of amphiphilic comb-like copolymers

    Institute of Scientific and Technical Information of China (English)

    冯莺; 隋家贤; 赵季若; 陈欣方

    2000-01-01

    Micellar behaviors in 2D and 3D lattice models for amphiphilic comb-like copolymers in water phase and in water/oil mixtures were simulated. A dynamical algorithm together with chain reptation movements was used in the simulation. Three-dimension displaying program was pro-grammed and free energy was estimated by Monte Carlo technigue. The results demonstrate that reduced interaction energy influences morphological structures of micelle and emulsion ??stems greatly; 3D simulation showing can display more direct images of morphological structures; the amphiphilic comb-like polymers with a hydrophobic main chain and hydrophilic side chains have lower energy in water than in oil.

  12. 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.

  13. Intra-chain organisation of hydrophobic residues controls inter-chain aggregation rates of amphiphilic polymers

    CERN Document Server

    Varilly, Patrick; Kirkegaard, Julius B; Knowles, Tuomas P J; Chandler, David

    2016-01-01

    Aggregation of amphiphiles through the action of hydrophobic interactions is a common feature in soft condensed matter systems and is of particular importance in the context of biophysics as it underlies both the generation of functional biological machinery as well as the formation of pathological misassembled states of proteins. Here we explore the aggregation behaviour of amphiphilic polymers using lattice Monte-Carlo calculations and show that the distribution of hydrophobic residues within the polymer sequence determines the facility with which dry/wet interfaces can be created and that such interfaces drive the aggregation process.

  14. Soft metal ions, Cd(II) and Hg(II), induce triple-stranded alpha-helical assembly and folding of a de novo designed peptide in their trigonal geometries.

    OpenAIRE

    Li, X; K. Suzuki; Kanaori, K; Tajima, K; Kashiwada, A.; Hiroaki, H; Kohda, D; Tanaka, T

    2000-01-01

    We previously reported the de novo design of an amphiphilic peptide [YGG(IEKKIEA)4] that forms a native-like, parallel triple-stranded coiled coil. Starting from this peptide, we sought to regulate the assembly of the peptide by a metal ion. The replacement of the Ile18 and Ile22 residues with Ala and Cys residues, respectively, in the hydrophobic positions disrupted of the triple-stranded alpha-helix structure. The addition of Cd(II), however, resulted in the reconstitution of the triple-str...

  15. 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

  16. 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.

  17. Allosterically Regulated Phosphatase Activity from Peptide-PNA Conjugates Folded Through Hybridization.

    Science.gov (United States)

    Machida, Takuya; Dutt, Som; Winssinger, Nicolas

    2016-07-18

    The importance of spatial organization in short peptide catalysts is well recognized. We synthesized and screened a library of peptides flanked by peptide nucleic acids (PNAs) such that the peptide would be constrained in a hairpin loop upon hybridization. A screen for phosphatase activity led to the discovery of a catalyst with >25-fold rate acceleration over the linear peptide. We demonstrated that the hybridization-enforced folding of the peptide is necessary for activity, and designed a catalyst that is allosterically controlled using a complementary PNA sequence. PMID:27320214

  18. Artificial Hydrolase Based on Short Peptides Self-and Co-assembly Nanofiber†%基于短肽自组装与共组装的纳米纤维人工水解酶

    Institute of Scientific and Technical Information of China (English)

    吕昱琦; 王梦凡; 齐崴; 苏荣欣; 何志敏

    2015-01-01

    将水解酶活性中心催化三联体氨基酸( His/Ser/Asp)引入9-芴亚甲氧羰基苯丙氨酸二肽( Fmoc-FF)双亲短肽序列中,利用短肽的自组装性能,构建了具有对硝基苯酚乙酸酯水解活性的超分子纳米纤维人工水解酶.研究结果表明,形成规则的纳米纤维结构是获得催化活性的必要条件.9-芴亚甲氧羰基( Fmoc)基团间的弱相互作用促使β-折叠二级结构的形成.通过对比天然水解酶的米氏动力学方程、最适催化温度及pH结果可知,所制备的超分子纳米纤维人工水解酶具有与天然酶相似的酶学性质.金属离子Ca2+和Ba2+对人工水解酶活性具有激活作用,而Mg2+, Ni2+, Co2+, Cu2+和Zn2+则抑制酶活性.%The catalytic triad( Ser/His/Asp) of natural hydrolase were introduced into the peptide segment of 9-fluorenylmethoxycarbonyl-diphenylalanine( Fmoc-FF) , 9-fluorenylmethoxycarbonyl-phenylalanine-phenylala-nine-histidine(Fmoc-FFH), 9-fluorenylmethoxycarbonyl-phenylalanine-phenylalanine-serine(Fmoc-FFS) and 9-fluorenylmethoxycarbonyl-phenylalanine-phenylalanine-aspartate( Fmoc-FFD) were designed to construct the artificial hydrolase. Based on the self-assembly and co-assembly of Fmoc-peptides, a series of supramole-cular nanofibers built from the self-assembly of Fmoc-FFH( SA-H) , self-assembly of Fmoc-FFS( SA-S) , self-assembly of Fmoc-FFD( SA-D) , co-assembly of Fmoc-FFH and Fmoc-FFS( CoA-HS) , co-assembly of Fmoc-FFH and Fmoc-FFD( CoA-HD) , co-assembly of Fmoc-FFD and Fmoc-FFS( CoA-DS) , co-assembly of Fmoc-FFH, Fmoc-FFD and Fmoc-FFS ( CoA-HDS ) were obtained as artificial hydrolases. SA-H exhibited the highest hydrolysis activity for p-nitrophenyl acetate ( PNPA ) . It was found that the well-ordered structure of nanofiber is important for catalytic activity, and theβ-sheet structure come from the week interactions between Fmoc groups. The kinetics behavior, optimum temperature and pH studies showed the typical enzymatic cha

  19. Polymer-based vehicles for therapeutic peptide delivery.

    Science.gov (United States)

    Zhang, Jinjin; Desale, Swapnil S; Bronich, Tatiana K

    2015-01-01

    During the last decades increasing attention has been paid to peptides as potential therapeutics. However, clinical applications of peptide drugs suffer from susceptibility to degradation, rather short circulation half-life, limited ability to cross physiological barriers and potential immunogenicity. These challenges can be addressed by using polymeric materials as peptide delivery systems, owing to their versatile structures and properties. A number of polymer-based vehicles have been developed to stabilize the peptides and to control their release rates. Unfortunately, no single polymer or formulation strategy has been considered ideal for all types of peptide drugs. In this review, currently used and potential polymer-based systems for the peptide delivery will be discussed.

  20. Temporin-SHf, a New Type of Phe-rich and Hydrophobic Ultrashort Antimicrobial Peptide*

    OpenAIRE

    Abbassi, Feten; Lequin, Olivier; Piesse, Christophe; Goasdoué, Nicole; Foulon, Thierry; Nicolas, Pierre; Ladram, Ali

    2010-01-01

    Because issues of cost and bioavailability have hampered the development of gene-encoded antimicrobial peptides to combat infectious diseases, short linear peptides with high microbial cell selectivity have been recently considered as antibiotic substitutes. A new type of short antimicrobial peptide, designated temporin-SHf, was isolated and cloned from the skin of the frog Pelophylax saharica. Temporin-SHf has a highly hydrophobic sequence (FFFLSRIFa) and possesses the highest percentage of ...

  1. Resilient self-assembling hydrogels from block copolypeptide amphiphiles

    Science.gov (United States)

    Nowak, Andrew Paul

    The ability to produce well defined synthetic polypeptides has been greatly improved by the discovery of transition metal species that mediate the controlled polymerization of N-carboxyanhydrides (NCAs). These metal species create a living polymerization system by producing control over chain length, low polydispersities, and the ability to form complex block architectures. We have applied this system to the synthesis of block copolypeptide amphiphiles. Initial block copolymers synthesized were composed of hydrophilic, cationic poly(L-Lysine) combined with hydrophobic, alpha-helical poly(L-Leucine). These Lysine- block-Leucine copolypeptides were found to form stiff, clear hydrogels at low concentration (˜1 wt%) in low ionic strength water. Based on this unexpected result we used the flexibility of our transition metal polymerization chemistry to better understand the nature and mechanisms of gel formation in these materials. Systematic changes to the original Lysine-block-Leucine copolypeptides were made by altering overall chain size, relative block length, polyelectrolyte charge, and hydrophobic secondary structure. Rheological characterization revealed that the strength of these hydrogels was primarily dependent on degree of polymerization, relative block length, and a well ordered secondary structure in the hydrophobic segment. The Lysine-block-Leucine hydrogels were formed by direct addition of water to dry polypeptide material which swelled to homogeneously fill the entire volume of liquid with no special processing. CryoTEM showed a percolating cellular network at ˜100nm that appears to be comprised of both membranes and fibers. Larger length scales studied with Laser Scanning Confocal Microscopy revealed a spontaneously formed microporous network with large (˜10mum) water rich voids. These hydrogels also displayed interesting mechanical properties including rapid recovery of solid like behavior after being sheared to a liquid and mechanical stability

  2. Amphiphilic semi-interpenetrating polymer networks using pulverized rubber

    Science.gov (United States)

    Shahidi, Nima

    Scrap rubber materials provide a significant challenge to either reuse or safe disposal. Every year, millions of tires are discarded to landfills in the United States, consuming a staggering amount of land space, creating a high risk for large fires, breeding mosquitoes that spread diseases, and wasting the planet's natural resources. This situation cannot be sustained. The challenge of reusing scrap rubber materials is mainly due to the crosslinked structure of vulcanized rubber that prevent them from melting and further processing for reuse. The most feasible recycling approach is believed to be a process in which the vulcanized rubber is first pulverized into a fine powder and then incorporated into new products. The production of fine rubber particles is generally accomplished through the use of a cryogenic process that is costly. Therefore, development of a cost effective technology that utilizes a large quantity of the scrap rubber materials to produce high value added materials is an essential element in maintaining a sustainable solution to rubber recycling. In this research, a cost effective pulverization process, solid state shear extrusion (SSSE), was modified and used for continuous pulverization of the rubber into fine particles. In the modified SSSE process, pulverization takes place at high compressive shear forces and a controlled temperature. Furthermore, an innovative particle modification process was developed to enhance the chemical structure and surface properties of the rubber particles for manufacturing of high value added products. Modification of rubber particles was accomplished through the polymerization of a hydrophilic monomer mixture within the intermolecular structure of the hydrophobic rubber particles. The resulting composite particles are considered as amphiphilic particulate phase semi-interpenetrating polymer networks (PPSIPNs). The modified rubber particles are water dispersible and suitable for use in a variety of aqueous media

  3. 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.

  4. Simultaneous alignment and clustering of peptide data using a Gibbs sampling approach

    DEFF Research Database (Denmark)

    Andreatta, Massimo; Lund, Ole; Nielsen, Morten

    2013-01-01

    peptide datasets, however, is a complex task, especially when the data contain multiple receptor binding motifs, and/or the motifs are found at different locations within distinct peptides.Results: The algorithm presented in this article, based on Gibbs sampling, identifies multiple specificities......Motivation: Proteins recognizing short peptide fragments play a central role in cellular signaling. As a result of high-throughput technologies, peptide-binding protein specificities can be studied using large peptide libraries at dramatically lower cost and time. Interpretation of such large...... in peptide data by performing two essential tasks simultaneously: alignment and clustering of peptide data. We apply the method to de-convolute binding motifs in a panel of peptide datasets with different degrees of complexity spanning from the simplest case of pre-aligned fixed-length peptides to cases...

  5. PARTITION-OPTIMIZED SINGLE EMULSION PARTICLES IMPROVE SUSTAINED RELEASE OF AMPHIPHILIC BUMPED KINASE INHIBITORS TO CONTROL MALARIA TRANSMISSION

    Directory of Open Access Journals (Sweden)

    Christina Yacoob

    2015-11-01

    Full Text Available Amphiphilic molecules are challenging to be incorporatedinto polymeric particles for sustained release due to their significant solubility in both water and organic solvent used in the fabrication process. Here, we investigated an extensive panel of fabrication methods for the incorporation and release of amphiphilic molecules, in particular, novel amphiphilic bumped kinase inhibitors (BKIs. Previously, BKIswere shown to reduce malaria transmission by blocking of gametocyte exflagellation. Prolonged BKI bioavailability for effective transmission blocking is crucial since infectious gametocytes circulate for several weeks inthe mammalian host, well beyond the half-life of BKIs. So far, delivery systems for sustained release of those BKIs have not been successfully formulated yet. Here we demonstrate that out of several delivery vehicles the partition-optimized single emulsion particles are the ideal system for incorporation and sustained release of amphiphilic BKIs. They increased the incorporation greater than 90% through optimized partitioning of amphiphilic molecules to the polymer phase and sustained release of BKIs up to several weeks with a reduction in the initial burst release. Overall this work provides a method for the incorporation and sustained release of amphiphilic BKIs, and can be adapted for other amphiphilic molecules.

  6. 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.

  7. Unimolecular micelles of amphiphilic cyclodextrin-core star-like block copolymers for anticancer drug delivery.

    Science.gov (United States)

    Xu, Zhigang; Liu, Shiying; Liu, Hui; Yang, Cangjie; Kang, Yuejun; Wang, Mingfeng

    2015-11-11

    Well-defined star-like amphiphilic polymers composed of a β-cyclodextrin core, from which 21 hydrophobic poly(lactic acid) arms and hydrophilic poly(ethylene glycol) arms are grafted sequentially, form robust and uniform unimolecular micelles that are biocompatible and efficient in the delivery of anticancer drugs. PMID:26121632

  8. Bilayer Vesicles of Amphiphilic Cyclodextrins: Host Membranes That Recognize Guest Molecules

    NARCIS (Netherlands)

    Falvey, Patrick; Lim, Choon Woo; Darcy, Raphael; Revermann, Tobias; Karst, Uwe; Giesbers, Marcel; Marcelis, Antonius T.M.; Lazar, Adina; Coleman, Anthony W.; Reinhoudt, David N.; Ravoo, Bart Jan

    2005-01-01

    A family of amphiphilic cyclodextrins (6, 7) has been prepared through 6-S-alkylation (alkyl=n-dodecyl and n-hexadecyl) of the primary side and 2-O-PEGylation of the secondary side of a-, B-, and Y-cyclodextrins (PEG=poly(ethylene glycol)). These cyclodextrins form nonionic bilayer vesicles in aqueo

  9. New carbon-carbon linked amphiphilic carboranyl-porphyrins as boron neutron capture agents

    International Nuclear Information System (INIS)

    Novel amphiphilic carboranyl-porphyrins have been synthesized for Boron Neutron Capture Therapy (BNCT). These compounds have carbon-carbon bonds between the carborane residues and the porphyrin meso-phenyl groups, and contain 28-31% boron by weight . (author)

  10. Preparation of Vesicles and Nanoparticles of Amphiphilic Cyclodextrins Containing Labile Disulfide Bonds

    NARCIS (Netherlands)

    Nolan, Darren; Darcy, Raphael; Ravoo, Bart Jan

    2003-01-01

    Amphiphilic cyclodextrin derivatives were prepared in which a disulfide bond connects the hydrophobic substituents to the macrocycle. These compounds were obtained by 1,3-dicyclohexylcarbodiimide-mediated coupling reactions of heptakis(6-amino-6-deoxy)-B-cyclodextrins and disulfide-containing carbox

  11. 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

    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...

  12. Gold Nanoparticles Protected with Thiol-Derivatized Amphiphilic Poly(epsilon-caprolactone)-b-poly(acrylic acid)

    DEFF Research Database (Denmark)

    Javakhishvili, Irakli; Hvilsted, Søren

    2009-01-01

    Amphiphilic poly(epsilon-caprolactone)-b-poly(acrylic acid) (HS-PCL-b-PAA) with a thiol functionality in the PCL terminal has been prepared in a novel synthetic cascade. Initially, living anionic ring-opening polymerization (ROP) of epsilon-caprolactone (epsilon-CL) employing the difunctional...

  13. Tunable Hydrophobicity in DNA Micelles : Design, Synthesis, and Characterization of a New Family of DNA Amphiphiles

    NARCIS (Netherlands)

    Anaya, Milena; Kwak, Minseok; Musser, Andrew J.; Muellen, Klaus; Herrmann, Andreas; Müllen, Klaus

    2010-01-01

    This work describes the synthesis and characterization of a new family of DNA amphiphiles containing modified nucleobases. The hydrophobicity was imparted by the introduction of a dodec-1-yne chain at the 5-position of the uracil base, which allowed precise and simple tuning of the hydrophobic prope

  14. 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(st...

  15. Inducing spin crossover in metallo-supramolecular polyelectrolytes through an amphiphilic phase transition.

    Science.gov (United States)

    Bodenthin, Yves; Pietsch, Ullrich; Möhwald, Helmuth; Kurth, Dirk G

    2005-03-01

    A phase transition in an amphiphilic mesophase is explored to deliberately induce mechanical strain in an assembly of tightly coupled metal ion coordination centers. Melting of the alkyl chains in the amphiphilic mesophase causes distortion of the coordination geometry around the central transition metal ion. As a result, the crystal field splitting of the d-orbital subsets decreases resulting in a spin transition from a low-spin to a high-spin state. The diamagnetic-paramagnetic transition is reversible. This concept is demonstrated in a metallo-supramolecular coordination polyelectrolyte-amphiphile complex self-assembled from ditopic bis-terpyridines, Fe(II) as central transition metal, and dialkyl phosphates as amphiphiles. The magnetic properties are studied in a Langmuir-Blodgett multilayer. The modularity of this concept provides extensive control of structure and function from molecular to macroscopic length scales and gives access to a wide range of new molecular magnetic architectures such as nanostructures, thin films, and liquid crystals. PMID:15740150

  16. Transfection of small numbers of human endothelial cells by electroporation and synthetic amphiphiles

    NARCIS (Netherlands)

    van Leeuwen, E B; van der Veen, A Y; Hoekstra, D; Engberts, J B; Halie, M R; van der Meer, J; Ruiters, M H

    1999-01-01

    OBJECTIVES: This study compared the efficiency of electroporation and synthetic amphiphiles. (SAINT-2pp/DOPE) in transfecting small numbers of human endothelial cells. METHODS AND RESULTS: Optimal transfection conditions were tested and appeared to be 400 V and 960 microF for electroporation and a 1

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

    NARCIS (Netherlands)

    Niazi, Muhammad Bilal Khan; Broekhuis, Antonius A.

    2016-01-01

    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 i

  18. Bilayer vesicles of amphiphilic cyclodextrines: host membranes that recognize guest molecules

    NARCIS (Netherlands)

    Falvey, P.; Lim, C.W.; Darcy, R.; Revermann, T.; Karst, U.; Marcelis, A.T.M.; Coleman, A.W.; Reinhoudt, D.N.; Ravoo, B.J.

    2005-01-01

    A family of amphiphilic cyclodextrins (6, 7) has been prepared through 6-S-alkylation (alkyl=n-dodecyl and n-hexadecyl) of the primary side and 2-O-PEGylation of the secondary side of alpha-, beta-, and gamma-cyclodextrins (PEG=poly(ethylene glycol)). These cyclodextrins form nonionic bilayer vesicl

  19. SYNTHESIS OF AMPHIPHILIC COMB-SHAPED COPOLYMERS USED FOR SURFACE MODIFICATION OF PVDF MEMBRANES

    Institute of Scientific and Technical Information of China (English)

    Jian-hua Li; You-yi Xu; Jian-hua Wang; Chun-hui Du

    2009-01-01

    The synthesis of a novel amphiphilic comb-shaped copolymer consisting of a main chain of styrene-(N-(4-hydroxyphenyl) maleimide) (SHMI) copolymer and poly(ethylene glycol) methyl ether methacrylate (PEGMA) side groups was achieved by atom transfer radical polymerization (ATRP). The amphiphilic copolymers were characterized by ~1H-NMR, Fourier transform infrared (FTIR) spectroscopy and gel permeation chromatography (GPC). From thermogravimetric analysis (TGA), the decomposition temperature of SHMI-g-PEGMA is lower than that of SHMI, and the graft ratio of PEGMA in the SHMI is 18.6%. The experimental results of solubilities showed that SHMI, SHMI-Br and SHMI-g-PEGMA had excellent solubility in polar solvents, such as DMF, DMSO and NMP. SHMI-g-PEGMA had higher solubilities in H_2O and methanol, while lower solubility in CHCl_3 than SHMI and SHMI-Br. PVDF blend membranes were prepared via the standard immersion precipitation phase inversion process, using amphiphilic SHMI-g-PEGMA copolymer as additives. The morphology and hydrophilicity of the blend membrane surfaces were characterized by SEM and water contact angle. It is demonstrated that the blend membranes display enhanced hydrophilicity compared to unmodified PVDF membranes. Finally, the permeation and anti-fouling properties were investigated. The result shows that amphiphilic SHMI-g-PEGMA copolymer increases the permeatability and anti-fouling property of PVDF membranes greatly.

  20. Short Review

    DEFF Research Database (Denmark)

    Lynnerup, Niels; Rühli, Frank

    2015-01-01

    modality in ancient mummy research. The aim of this short review is to address the advantages and pitfalls of this particular technique for such unique samples. We recommend that when results of X-ray examination of mummies are presented, the specific recording data should be listed, and any given finds...

  1. Short fusion

    CERN Multimedia

    2002-01-01

    French and UK researchers are perfecting a particle accelerator technique that could aid the quest for fusion energy or make X-rays that are safer and produce higher-resolution images. Led by Dr Victor Malka from the Ecole Nationale Superieure des Techniques Avancees in Paris, the team has developed a better way of accelerating electrons over short distances (1 page).

  2. Nucleation, growth, and dissolution of Ag nanostructures formed in nanotubular J-aggregates of amphiphilic cyanine dyes

    CERN Document Server

    Polzer, Egon Steeg Frank; Qiao, Yan; Rabe, Jürgen P; Kirstein, Stefan

    2015-01-01

    The nucleation, growth, and dissolution of silver nanowires within tubular aggregates of the dye C8S3 are investigated. The tubular aggregates are formed in aqueous solution from amphiphilic dyes and the silver wires are grown from silver salt. Samples were investigated systematically and in detail using cryo-TEM and TEM at different time steps after addition of silver salt (AgNO3) and short illumination with blue light (420 nm) for production of nuclei. The enhanced concentration of silver ions in proximity of the aggregates surface leads to favoured growth of seeds at or within the aggregates. The early stage of the seed growth is observable by cryo-TEM and shows to be well separated and isolated. There are no indications that nuclei are formed at preferred defect sites at the aggregates which is interpreted as homogeneous nucleation. The spatial position of the majority of initially formed seeds discriminates between growth of particles at the outer surface of the aggregate or wires at the inner space. The...

  3. Preparation of amphiphilic glycopolymers with flexible long side chain and their use as stabilizer for emulsion polymerization.

    Science.gov (United States)

    Alvárez-Paino, Marta; Juan-Rodríguez, Rafael; Cuervo-Rodríguez, Rocío; Muñoz-Bonilla, Alexandra; Fernández-García, Marta

    2014-03-01

    A glycomonomer was synthesized from poly(ethylene glycol) methacrylate (PEGMA). The terminal hydroxyl moieties were activated with ester groups and subsequently the glucosamine was incorporated forming urethane linkages. The obtained glycomonomer was copolymerized with methyl acrylate by free radical polymerization varying the initial feed composition to produce different amphiphilic glycopolymers. The glycopolymers were then characterized and compared with the homologous glycopolymers based on 2-{[(D-glucosamin-2-N-yl)carbonyl]oxy}ethyl methacrylate. Both series of glycopolymers were used in emulsion polymerization of methyl acrylate as stabilizers without the addition of any cosurfactant. Although high conversions were not achieved with any of the employed surfactant, the glycopolymers provide good colloidal stability, spherical, monodisperse and small latex particles in comparison with the surfactant-free emulsion polymerization. The latex particles stabilized with the glycosurfactant based on PEGMA, containing a flexible spacer between the backbone and the glucosamine, lead to smooth films whereas the short side chain surfactant from 2-hydroxyethyl methacrylate (HEMA), with higher glass transition temperature, restricts the coalescence of particles and, therefore, the film formation. Moreover, the surface bioactivity of these polymer coatings was examined by analyzing their specific interaction with the lectin, Concanavalin A, Canavalia ensiformis. The specific and successful binding to the Concanavalin A was demonstrated by fluorescence microscopy for both series being more intense with increasing amount of glycounits in the glycopolymer stabilizers. Interestingly, the incorporation of a flexible spacer in the glycopolymer structures enhances the binding activity.

  4. Plant signalling peptides

    OpenAIRE

    Wiśniewska, Justyna; Trejgell, Alina; Tretyn, Andrzej

    2003-01-01

    Biochemical and genetic studies have identified peptides that play crucial roles in plant growth and development, including defence mechanisms in response to wounding by pests, the control of cell division and expansion, and pollen self-incompatibility. The first two signalling peptides to be described in plants were tomato systemin and phytosulfokine (PSK). There is also biochemical evidence that natriuretic peptide-like molecules, immunologically-relatedt o those found ...

  5. Polycyclic peptide therapeutics.

    Science.gov (United States)

    Baeriswyl, Vanessa; Heinis, Christian

    2013-03-01

    Owing to their excellent binding properties, high stability, and low off-target toxicity, polycyclic peptides are an attractive molecule format for the development of therapeutics. Currently, only a handful of polycyclic peptides are used in the clinic; examples include the antibiotic vancomycin, the anticancer drugs actinomycin D and romidepsin, and the analgesic agent ziconotide. All clinically used polycyclic peptide drugs are derived from natural sources, such as soil bacteria in the case of vancomycin, actinomycin D and romidepsin, or the venom of a fish-hunting coil snail in the case of ziconotide. Unfortunately, nature provides peptide macrocyclic ligands for only a small fraction of therapeutic targets. For the generation of ligands of targets of choice, researchers have inserted artificial binding sites into natural polycyclic peptide scaffolds, such as cystine knot proteins, using rational design or directed evolution approaches. More recently, large combinatorial libraries of genetically encoded bicyclic peptides have been generated de novo and screened by phage display. In this Minireview, the properties of existing polycyclic peptide drugs are discussed and related to their interesting molecular architectures. Furthermore, technologies that allow the development of unnatural polycyclic peptide ligands are discussed. Recent application of these technologies has generated promising results, suggesting that polycyclic peptide therapeutics could potentially be developed for a broad range of diseases. PMID:23355488

  6. Large organized surface domains self-assembled from nonpolar amphiphiles.

    Science.gov (United States)

    Krafft, Marie Pierre

    2012-04-17

    For years, researchers had presumed that Langmuir monolayers of small C(n)F(2n+1)C(m)H(2m+1) (FnHm) diblock molecules (such as F8H16) consisted of continuous, featureless films. Recently we have discovered that they instead form ordered arrays of unusually large (~30-60 nm), discrete self-assembled surface domains or hemimicelles both at the surface of water and on solid substrates. These surface micelles differ in several essential ways from all previously reported or predicted molecular surface aggregates. They self-assemble spontaneously, even at zero surface pressure, depending solely on a critical surface concentration. They are very large (~100 times the length of the diblock) and involve thousands of molecules (orders of magnitude more than classical micelles). At the same time, the surface micelles are highly monodisperse and self-organize in close-packed hexagonal patterns (two-dimensional crystals). Their size is essentially independent from pressure, and they do not coalesce and are unexpectedly sturdy for soft matter (persisting even beyond surface film collapse). We and other researchers have observed large surface micelles for numerous diblocks, using Langmuir-Blodgett (LB) transfer, spin-coating and dip-coating techniques, or expulsion from mixed monolayers, and on diverse supports, establishing that hemimicelle formation and ordering are intrinsic properties of (perfluoroalkyl)alkanes. Notably, they involve "incomplete" surfactants with limited amphiphilic character, which further illustrates the outstanding capacity for perfluoroalkyl chains to promote self-assembly and interfacial film structuring. Using X-ray reflectivity, we determined a perfluoroalkyl-chain-up orientation. Theoretical investigations assigned self-assembly and hemimicelle stability to electrostatic dipole-dipole interactions at the interface between Fn- and Hm-sublayers. Grazing-incidence small-angle X-ray scattering (GISAXS) data collected directly on the surface of water

  7. Structure and reactions in some amphiphilic association systems

    Science.gov (United States)

    Guo, Rong

    1999-06-01

    surfactant CTAB system with various co-surfactants: n-pentanol, n-octanol, n-valeric acid, and n-caproic acid, but not in SDS or Triton X-100 systems. Presence of VC stabilizes both W/O and O/W microemulsions but destabilizes the lamellar liquid crystalline phase. Hence, the "phase transition" from the lamellar liquid crystalline phase to the isotropic phase of O/W, W/O and bicontinuous structure phase occurs with the addition of VC. The hydrotropic action of VC has been used in sunscreens to increase the solubility of sunscreen E 557. The UV absorption spectra of E557 in various media surprisingly had a dependence on the colloid structure. A new method, the preparation of water-soluble nanoparticles, has been found by employing the effect of the penetration of solvent from water layer to amphiphilic layer in lamellar liquid crystals on the solubility of inorganic salts. Water-insoluble nanoparticles have been synthesized by the reaction of two water-soluble inorganic salts in the lamellar liquid crystal. The particle size is less than 10nm and can be controlled by the thickness of the solvent layer in the lamellar liquid crystal. The lamellar liquid crystalline phase of the Triton X-100/decanol/water system has been chosen as a medium because of its large lamellar liquid crystal region and its stability when inorganic salts are added.

  8. Selection of the specific coalescent peptide of human CD59 by phage display techniques

    Institute of Scientific and Technical Information of China (English)

    YING CHENG; MEI HUA GAO; BING WANG; QIU BO WANG

    2006-01-01

    To screen and identify the short peptides with specific binding activity to human CD59 and to design the short-peptide clamp against tumor escape, the phage display peptide library containing 12 peptides was used to select the highly expressed specific coalescent peptide of human CD59 in CHO cells. Positive phage clones obtained after 5 rounds of biopanning and detected with ELISA were obtained, in which 8 of them with high binding activity to human CD59 were sequenced. The 3 sequences thus obtained showed high homology with each and certain homology with sequence with human CD2 (PubMed 339HGAAENSLSPSS), and all contained primary structure HXAXXXXXXPXX, of which this sequence may be the mimic conformational epitope binding to human CD59. These results in the present study may be helpful to design the short-peptide clamp against the active sites of CD59 on tumor escape.

  9. Self-Assembling Amphiphilic Siderophores from Marine Bacteria

    Science.gov (United States)

    Martinez, J. S.; Zhang, G. P.; Holt, P. D.; Jung, H.-T.; Carrano, C. J.; Haygood, M. G.; Butler, Alison

    2000-02-01

    Most aerobic bacteria secrete siderophores to facilitate iron acquisition. Two families of siderophores were isolated from strains belonging to two different genera of marine bacteria. The aquachelins, from Halomonas aquamarina strain DS40M3, and the marinobactins, from Marinobacter sp. strains DS40M6 and DS40M8, each contain a unique peptidic head group that coordinates iron(III) and an appendage of one of a series of fatty acid moieties. These siderophores have low critical micelle concentrations (CMCs). In the absence of iron, the marinobactins are present as micelles at concentrations exceeding their CMC; upon addition of iron(III), the micelles undergo a spontaneous phase change to form vesicles. These observations suggest that unique iron acquisition mechanisms may have evolved in marine bacteria.

  10. Lipid-peptide vesicle nanoscale hybrids for triggered drug release by mild hyperthermia in vitro and in vivo.

    Science.gov (United States)

    Al-Ahmady, Zahraa S; Al-Jamal, Wafa' T; Bossche, Jeroen V; Bui, Tam T; Drake, Alex F; Mason, A James; Kostarelos, Kostas

    2012-10-23

    The present study describes leucine zipper peptide-lipid hybrid nanoscale vesicles engineered by self-assembled anchoring of the amphiphilic peptide within the lipid bilayer. These hybrid vesicles aim to combine the advantages of traditional temperature-sensitive liposomes (TSL) with the dissociative, unfolding properties of a temperature-sensitive peptide to optimize drug release under mild hyperthermia, while improving in vivo drug retention. The secondary structure of the peptide and its thermal responsiveness after anchoring onto liposomes were studied with circular dichroism. In addition, the lipid-peptide vesicles (Lp-peptide) showed a reduction in bilayer fluidity at the inner core, as observed with DPH anisotropy studies, while the opposite effect was observed with an ANS probe, indicating peptide interactions with both the headgroup region and the hydrophobic core. A model drug molecule, doxorubicin, was successfully encapsulated in the Lp-peptide vesicles at higher than 90% efficiency following the remote loading, pH-gradient methodology. The release of doxorubicin from Lp-peptide hybrids in vitro indicated superior serum stability at physiological temperatures compared to lysolipid-containing temperature-sensitive liposomes (LTSL) without affecting the overall thermo-responsive nature of the vesicles at 42 °C. A similar stabilizing effect was observed in vivo after intravenous administration of the Lp-peptide vesicles by measuring (14)C-doxorubicin blood kinetics that also led to increased tumor accumulation after 24 h. We conclude that Lp-peptide hybrid vesicles present a promising new class of TSL that can offer previously unexplored opportunities for the development of clinically relevant mild hyperthermia-triggered therapeutic modalities.

  11. 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 ...

  12. 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.

  13. Peptide Nucleic Acids

    DEFF Research Database (Denmark)

    2004-01-01

    A novel class of compounds known as peptide nucleic acids, bind complementary DNA and RNA strands, and generally do so more strongly than the corresponding DNA or RNA strands while exhibiting increased sequence specificity and solubility. The peptide nucleic acids comprise ligands selected from...

  14. 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.

  15. 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.

  16. Synthesis of a new generation of amphiphiles with multi-cryptand headgroups: A comparative study at air–water interface

    Indian Academy of Sciences (India)

    B Sarkar; R K Gupta; R A Singh; P K Bharadwaj

    2008-06-01

    A laterally non-symmetric aza cryptand has been derivatized with two hydrophobic chains to afford amphiphiles with one cryptand headgroup and two hydrophobic tails. Three such units readily attach to 1,3,5-benzenetricarbonyl trichloride, to form a new generation of amphiphilic molecules with three cryptand headgroups and six hydrophobic chains. These molecules are studied at the air–water interface in a Langmuir trough. They readily form LB-films on a number of substrates that are characterized.

  17. 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.

  18. Short esophagus.

    Science.gov (United States)

    Kunio, Nicholas R; Dolan, James P; Hunter, John G

    2015-06-01

    In the presence of long-standing and severe gastroesophageal reflux disease, patients can develop various complications, including a shortened esophagus. Standard preoperative testing in these patients should include endoscopy, esophagography, and manometry, whereas the objective diagnosis of a short esophagus must be made intraoperatively following adequate mediastinal mobilization. If left untreated, it is a contributing factor to the high recurrence rate following fundoplications or repair of large hiatal hernias. A laparoscopic Collis gastroplasty combined with an antireflux procedure offers safe and effective therapy.

  19. Application of Collagen-Model Triple-Helical Peptide-Amphiphiles for CD44-Targeted Drug Delivery Systems

    OpenAIRE

    Ndinguri, Margaret W.; Alexander Zheleznyak; Lauer, Janelle L.; Anderson, Carolyn J.; Fields, Gregg B.

    2012-01-01

    Cancer treatment by chemotherapy is typically accompanied by deleterious side effects, attributed to the toxic action of chemotherapeutics on proliferating cells from nontumor tissues. The cell surface proteoglycan CD44 has been recognized as a cancer stem cell marker. The present study has examined CD44 targeting as a way to selectively deliver therapeutic agents encapsulated inside colloidal delivery systems. CD44/chondroitin sulfate proteoglycan binds to a triple-helical sequence derived f...

  20. Characterization of peptide amphiphile nanofibers their interactions with chondroprogenitor cells and morphological analysis of tissues from transgenic animals

    OpenAIRE

    Tombuloğlu, Ayşegül

    2012-01-01

    Ankara : The Materials Science and Nanotechnology Program of the Graduate School of Engineering and Science of Bilkent Univ, 2012. Thesis (Master's) -- Bilkent University, 2012. Includes bibliographical references leaves 124-135. Tombuloğlu, Ayşegül Master's

  1. 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)

    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

  2. Proinsulin C-peptide interferes with insulin fibril formation

    Energy Technology Data Exchange (ETDEWEB)

    Landreh, Michael [Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 77 Stockholm (Sweden); Stukenborg, Jan-Bernd [Department of Women' s and Children' s Health, Astrid Lindgren Children' s Hospital, Pediatric Endocrinology Unit, Karolinska Institutet and University Hospital, S-17176 Stockholm (Sweden); Willander, Hanna [KI-Alzheimer' s Disease Research Center, NVS Department, Karolinska Institutet, S-141 86 Stockholm (Sweden); Soeder, Olle [Department of Women' s and Children' s Health, Astrid Lindgren Children' s Hospital, Pediatric Endocrinology Unit, Karolinska Institutet and University Hospital, S-17176 Stockholm (Sweden); Johansson, Jan [KI-Alzheimer' s Disease Research Center, NVS Department, Karolinska Institutet, S-141 86 Stockholm (Sweden); Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, S-751 23 Uppsala (Sweden); Joernvall, Hans, E-mail: Hans.Jornvall@ki.se [Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 77 Stockholm (Sweden)

    2012-02-17

    Highlights: Black-Right-Pointing-Pointer Insulin and C-peptide can interact under insulin fibril forming conditions. Black-Right-Pointing-Pointer C-peptide is incorporated into insulin aggregates and alters aggregation lag time. Black-Right-Pointing-Pointer C-peptide changes insulin fibril morphology and affects backbone accessibility. Black-Right-Pointing-Pointer C-peptide may be a regulator of fibril formation by {beta}-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 {beta}-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.

  3. Proinsulin C-peptide interferes with insulin fibril formation

    International Nuclear Information System (INIS)

    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.

  4. In silico designed of an Anticancer Peptide SVS-1 multipharmacophore as a potential drug-like efficator in Preceding Membrane Neutralization using a web server multi-mimotopic algorithmic approach for biclustering analysis of expression data.

    OpenAIRE

    Ioannis Grigoriadis

    2015-01-01

    Anticancer peptides (ACPs) are polycationic amphiphiles capable of preferentially killing a widespectrum of cancer cells relative to non-cancerous cells. Their primary mode of action is aninteraction with the cell membrane and subsequent activation of lytic effects, however it remainscontroversial the exact mechanism responsible for this mode of action. It has in previous studies been shown that utilizing zeta potential analyses it was possible to demonstrate the interaction of a small antica...

  5. Atomic force microscopy investigations of peptide self-assembly

    OpenAIRE

    Sedman, Victoria L.

    2006-01-01

    The ability of short peptide fragments to self-assemble in isolation as amyloid and amyloid-like structures has prompted their use as model systems for the study of amyloid formation and recently also for their utilisation as novel nanofibrillar material. The atomic force microscope (AFM) is used here to investigate the self-assembly of two peptide systems and the development of strategies to directly manipulate and control the structures they form. The studies presented in Chapter 2 addr...

  6. 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....

  7. Characterization of Fe3O4/P(St-MPEO) Amphiphilic Magnetic Polymer Microspheres

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Amphiphilic magnetic microspheres consisting of styrene and poly(ethylene oxide) macromonomer(MPEO) were prepared by dispersion copolymerization in the presence of Fe3O4 magnetic fluid in an ethanol/water medium. The sizes of the magnetic microspheres and their distribution were characterized by means of scanning electron microscopy(SEM). The surface morphology and the average surface roughness of the microspheres were investigated by virtue of atomic force microscopy(AFM). It was found that the microspheres exhibit microscopic phase-separate and the mean square surface roughness of the microspheres increases with increasing MPEO used in the copolymerization. The amphiphilic magnetic microspheres containing 0.4-3.5 mg/g hydroxyl groups could be prepared from MPEO with different concentrations and styrene.

  8. Removal of volatile organic compounds using amphiphilic cyclodextrin-coated polypropylene.

    Science.gov (United States)

    Lumholdt, Ludmilla; Fourmentin, Sophie; Nielsen, Thorbjørn T; Larsen, Kim L

    2014-01-01

    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. PMID:25550739

  9. 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.

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

    DEFF Research Database (Denmark)

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

    Recently, there has been an augmented focus on the increasing amount of pesticides, drug residues and endocrine disruptors present in waste and drinking water1. These pollutants represent a challenge in water purification since they may be hazardous to human health even in low doses2. Cyclodextrins...... 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....... (CDs) are known to be able to form inclusion complexes with a large range of the unwanted pollutantse.g. 3 but in order to utilise this ability to purify water, the CDs must be immobilised on a surface, for instance, a membrane filter. We have developed a simple and fast method...

  11. Sustained release of protein from poly(ethylene glycol) incorporated amphiphilic comb like polymers.

    Science.gov (United States)

    Srividhya, M; Preethi, S; Gnanamani, A; Reddy, B S R

    2006-12-01

    Amphiphilic comb like macromonomer containing hydrophilic poly(ethylene glycol) groups covalently linked to poly(hydromethyl siloxane) (PHMS) were prepared by hydrosilylation reaction. The epoxy reacting sites were introduced to this amphiphilic system by the reaction with allyl epoxy propyl ether (AEPE). Bovine serum albumin (BSA), a model protein drug was loaded to the PEG-PDMS system and very thin membranes were made from this macromonomer adopting solution casting technique. The in vitro protein release studies at various pH conditions showed a controlled release profile without exhibiting any initial burst. The control of the initial burst might be due to the strong linkages of the protein with the membrane and the aggregation of the protein at the surface. The morphology of the membrane before and after the protein release, and the mechanical strength were evaluated. The surface properties of the membrane were studied using the contact angle measurements. PMID:16930885

  12. REVIEWS OF TOPICAL PROBLEMS: Supermolecular liquid-crystalline structures in solutions of amphiphilic molecules

    Science.gov (United States)

    Vedenov, A. A.; Levchenko, E. B.

    1983-09-01

    This paper reviews the physical properties of liquid-crystalline phases arising in solutions containing molecules of amphiphilic substances. The basic characteristics of micelle formation in dilute solutions, models of sphere-disk or sphere-cylinder structural transformations, as well as phase transitions related to the appearance of lyotropic mesophases in the system, including nematic, lamellar, hexagonal, and others, are examined. The results of experimental and theoretical investigation of "solvation" forces acting between micelles in the solvent, as well as recently studied models of swelling of lamellar phases are presented. The phenomena occurring near the inversion point of microemulsions in amphiphile-oil-water systems are examined briefly. The role of liquid-crystalline ordering in some biological systems is discussed.

  13. Amphiphilic block copolymers in oil-water-surfactant mixtures: efficiency boosting, structure, phase behaviour and mechanism

    Science.gov (United States)

    Gompper, G.; Richter, D.; Strey, R.

    2001-10-01

    The effect of amphiphilic block copolymers on the phase behaviour and structure of ternary microemulsions in water, oil and non-ionic surfactant mixtures is reviewed. Recent experiments have revealed that the addition of small amounts of polyethylenepropylene-polyethyleneoxide block copolymer to the ternary systems leads to a dramatic increase in the volumes of oil and water solubilized into a bicontinuous microemulsion for a given surfactant volume fraction. While phase diagrams directly show the power of the amphiphilic block copolymers as efficiency boosters, the theoretical analysis in terms of bending energy discloses the mechanism for the efficiency boosting as due to the variation of the surfactant film curvature elasticity by tethered polymers in the form of mushrooms at the interface. Neutron scattering experiments employing a high-precision two-dimensional contrast variation technique confirm this picture and demonstrate that the polymer molecules uniformly decorate the surfactant film.

  14. Micelle assembly. Multidimensional hierarchical self-assembly of amphiphilic cylindrical block comicelles.

    Science.gov (United States)

    Qiu, Huibin; Hudson, Zachary M; Winnik, Mitchell A; Manners, Ian

    2015-03-20

    Self-assembly of molecular and block copolymer amphiphiles represents a well-established route to micelles with a wide variety of shapes and gel-like phases. We demonstrate an analogous process, but on a longer length scale, in which amphiphilic P-H-P and H-P-H cylindrical triblock comicelles with hydrophobic (H) or polar (P) segments that are monodisperse in length are able to self-assemble side by side or end to end in nonsolvents for the central or terminal segments, respectively. This allows the formation of cylindrical supermicelles and one-dimensional (1D) or 3D superstructures that persist in both solution and the solid state. These assemblies possess multiple levels of structural hierarchy in combination with existence on a multimicrometer-length scale, features that are generally only found in natural materials. PMID:25792323

  15. AMPHIPHILIC STAR-BLOCK COPOLYMERS BY IODIDE-MEDIATED RADICAL POLYMERIZATION

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Amphiphilic star-block copolymers composed of polystyrene and poly(acrylic acid) were synthesized by iodidemediated radical polymerization. Firstly, free radical polymerization of styrene was carried out with AIBN as initiator and 1,1,1-trimethyolpropane tri(2-iodoisobutyrate) as chain transfer agent, giving iodine atom ended star-shaped polystyrene with three arm chains, R(polystyrene)3. Secondly, tert-butyl acrylate was polymerization using polystyrene obtained as macro-chain transfer agent, and star-block copolymer, R(polystyrene-b-poly(tert-butyl acrylate))3 with controlled molecular weight was obtained. Finally, amphiphilic star-block copolymer, R(polystyrene-b-poly(acrylic acid))3 was obtained by hydrolysis of R(polystyrene-b-poly(tert-butyl acrylate))3 under acidic condition.

  16. 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.

  17. Replication of simulated prebiotic amphiphile vesicles controlled by experimental lipid physicochemical properties

    International Nuclear Information System (INIS)

    We present a new embodiment of the graded autocatalysis replication domain (GARD) for the growth, replication and evolution of lipid vesicles based on a semi-empirical foundation using experimentally measured kinetic values of selected extant lipid species. Extensive simulations using this formalism elucidated the details of the dependence of the replication and properties of the vesicles on the physicochemical properties and concentrations of the lipids, both in the environment and in the vesicle. As expected, the overall concentration and number of amphiphilic components strongly affect average replication time. Furthermore, variations in acyl chain length and unsaturation of vesicles also influence replication rate, as do the relative concentrations of individual lipid types. Understanding of the dependence of replication rates on physicochemical parameters opens a new direction in the study of prebiotic vesicles and lays the groundwork for future studies involving the competition between lipid vesicles for available amphiphilic monomers

  18. New synthetic amphiphilic polymers for steric protection of liposomes in vivo.

    Science.gov (United States)

    Torchilin, V P; Trubetskoy, V S; Whiteman, K R; Caliceti, P; Ferruti, P; Veronese, F M

    1995-09-01

    Carboxy group-terminated synthetic polymers--branched poly(ethylene glycol), poly(acryloylmorpholine), and poly(vinylpyrrolidone)--were made amphiphilic by derivatization with phosphatidyl ethanolamine via the terminal carboxy group and then incorporated into lecithin-cholesterol liposomes prepared by the detergent dialysis method. Following the biodistribution of liposomes in mice, all three polymers were shown to be effective steric protectors for liposomes and were able to sharply increase liposome circulation times in a concentration-dependent manner. The accumulation of liposomes in the liver decreases. The effects observed are similar to those found for liposomes modified with linear poly(ethylene glycol). At low polymer concentration, amphiphilic branched poly(ethylene glycol) seems to be the most effective liposome protector, most probably, because at the same molar content of anchoring groups, each attachment point carries two polymeric chains and doubles the quantity of liposome-grafted polymer comparing to linear poly(ethylene glycol).

  19. 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.)

  20. Comparison of Facially Amphiphilic versus Segregated Monomers in the Design of Antibacterial Copolymers

    OpenAIRE

    Gabriel, Gregory J.; Maegerlein, Janet A.; Nelson, Christopher F.; Dabkowski, Jeffrey M.; Eren, Tarik; Nüsslein, Klaus; Tew, Gregory N.

    2009-01-01

    A direct comparison of two strategies for designing antimicrobial polymers is presented. Previously, we published several reports on the use of facially amphiphilic (FA) monomers which led to polynorbornenes with excellent antimicrobial activities and selectivities. Our polymers obtained by copolymerization of structurally similar segregated monomers, in which cationic and non-polar moieties reside on separate repeat units, led to polymers with less pronounced activities. A wide range of poly...

  1. 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

    2016-02-01

    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

  2. Removal of volatile organic compounds using amphiphilic cyclodextrin-coated polypropylene

    OpenAIRE

    Ludmilla Lumholdt; Sophie Fourmentin; Nielsen, Thorbjørn T; Larsen, Kim L.

    2014-01-01

    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 mixt...

  3. Amphiphilic zein hydrolysate as a novel nano-delivery vehicle for curcumin.

    Science.gov (United States)

    Wang, Yong-Hui; Wang, Jin-Mei; Yang, Xiao-Quan; Guo, Jian; Lin, Yuan

    2015-08-01

    In this paper, we developed amphiphilic zein hydrolysate (ZH) as a novel delivery vehicle, which could be used for preparing curcumin (Cur) nanocomplexes. These ZH-Cur nanocomplexes exhibited spherical morphology with a monodisperse size distribution (oil-water interface, as confirmed by micelle formation and dynamic interfacial adsorption respectively. Fluorescence titration and FTIR results indicated the existence of strong hydrophobic interactions between ZH and Cur, which was responsible for the complexation. PMID:26134524

  4. Dynamic Ordering Transitions of Liquid Crystals Driven by Interfacial Complexes Formed Between Polyanions and Amphiphilic Polyamines

    OpenAIRE

    Kinsinger, Michael I.; Buck, Maren E.; de Campos, Fernando; Lynn, David M.; Abbott, Nicholas L.

    2008-01-01

    We report the design of an amphiphilic polyamine based on poly(2-alkenyl azlactone) (polymer 1) that strongly couples the formation of polyelectrolyte complexes at aqueous/liquid crystal (LC) interfaces to ordering transitions in the LC. We demonstrate that the addition of a strong anionic polyelectrolyte to aqueous solutions in contact with polymer 1-laden LC interfaces (prepared by Langmuir-Schaefer transfer of monolayers of polymer 1 onto micrometer-thick films of nematic LC) triggers orde...

  5. 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

    2016-02-01

    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

  6. Langmuir-Blodgett Films and Calcium Ion Coordination of Biliverdin and Its Amphiphilic Derivatives

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Monolayer formation and LB film fabrication of amphiphilic derivative of biliverdin 1,diododecyl biliverdinamide [B(CONHC12H25)2,2] at an air-water interface on pure water subphase and subphase containing calcium ion were investigated and compared with 1.The coordination in ordered molecular films is much different from that in bulk solution.The formation of ligand-calcium complex was confirmed by X-ray photoelectron spectroscopy.

  7. Bioinspired amphiphilic phosphate block copolymers as non-fluoride materials to prevent dental erosion

    OpenAIRE

    Lei, Yanda; Wang, Tongxin; Mitchell, James W; Zaidel, Lynette; Qiu, Jianhong; Kilpatrick-Liverman, LaTonya

    2014-01-01

    Inspired by the fact that certain natural proteins, e.g. casein phosphopeptide or amelogenin, are able to prevent tooth erosion (mineral loss) and to enhance tooth remineralization, a synthetic amphiphilic diblock copolymer, containing a hydrophilic methacryloyloxyethyl phosphate block (MOEP) and a hydrophobic methyl methacrylate block (MMA), was designed as a novel non-fluoride agent to prevent tooth erosion under acidic conditions. The structure of the polymer, synthesized by reversible add...

  8. Structure of adsorption layers of amphiphilic copolymers on inorganic or organic particle surfaces

    OpenAIRE

    Bulychev, Nikolay; Dervaux, Bart; Dimberger, Klaus; Zubov, Vitali; Du Prez, Filip; Eisenbach, Claus D

    2010-01-01

    The structure of adsorption layers of amphiphilic block and block-like copolymers of poly(isobornyl acrylate) and poly(acrylic acid) on the surface of hydrophilic titanium dioxide and hydrophobic copper phthalocyanine (CuPc) pigments in an aqueous studied by the electrokinetic sonic amplitude (ESA) method. The electroacoustic behaviour of the polyelectrolyte block copolymer-coated particles could be described in the context of the polymer gel layer theory. The polymer layer around the particl...

  9. Aggregate of Amphiphilic Block Copolymer as a Pseudo-Stationary Phase in Capillary Electrophoresis

    OpenAIRE

    Nakamura, Tohru; OHKI, Akira; Mishiro, Masaki; Tsuyashima, Osamu; Maeda, Shigeru; ナカムラ, トオル; オオキ, アキラ; ミシロ, マサキ; ツヤシマ, オサム; マエダ, シゲル; 中村, 透; 大木, 章; 艶島, 修; 前田, 滋

    1999-01-01

    The use of an aggregate of amphiphilic block copolymer 1, which consists of poly[(N-acetylimino)ethylene] and poly[(N-pentanoylimino)ethylene], for a pseudo-stationary phase in capillary electrophoresis has been examined. From gel-filtration chromatography, the aggregate from 1 (1-AG) was found to incorporate phenol. When the running solution contains 1-AG and sodium dodecyl sulfate (SDS), the electrophoretic mobility becomes nearly zero. Thus, it is found that when 1-AG and SDS are added to ...

  10. 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

    reversible addition–fragmentation chain transfer (RAFT) polymerization, copper-mediated atom transfer radical polymerization (ATRP), and a selective deprotection reaction. Initially, multifunctional ATRP macroinitiators based on PHEMA backbone are prepared by RAFT polymerization. Then ATRP......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...

  11. Synthesis and self-assembly of multiple thermoresponsive amphiphilic block copolymers

    OpenAIRE

    Weiß, Jan

    2011-01-01

    In the present thesis, the self-assembly of multi thermoresponsive block copolymers in dilute aqueous solution was investigated by a combination of turbidimetry, dynamic light scattering, TEM measurements, NMR as well as fluorescence spectroscopy. The successive conversion of such block copolymers from a hydrophilic into a hydrophobic state includes intermediate amphiphilic states with a variable hydrophilic-to-lipophilic balance. As a result, the self-organization is not following an all-or-...

  12. Novel amphiphilic diblock copolymers by RAFT-polymerization, their self-organization and surfactant properties

    OpenAIRE

    Garnier, Sébastien

    2006-01-01

    The Reversible Addition Fragmentation Chain Transfer (RAFT) process using the new RAFT agent benzyldithiophenyl acetate is shown to be a powerful polymerization tool to synthesize novel well-defined amphiphilic diblock copolymers composed of the constant hydrophobic block poly(butyl acrylate) and of 6 different hydrophilic blocks with various polarities, namely a series of non-ionic, non-ionic comb-like, anionic and cationic hydrophilic blocks. The controlled character of the polymerizations ...

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

    DEFF Research Database (Denmark)

    Monnard, Pierre-Alain

    2011-01-01

    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 amp...... network. References 1 Cape, J., et al. (2011) Chem. Sci., 2 (4), 661-667. 2 Maurer, S. E., et al. (2009) Astrobiology, 9, 979-987. 3 Caschera, F., et al. Langmuir, In press....

  14. Elisapterosin F: a polycyclic gorgonian-derived diterpene with a facially amphiphilic structure

    Science.gov (United States)

    Rodríguez, Ileana I.; Rodríguez, Abimael D.

    2009-01-01

    Analysis of the terpene metabolites of Pseudopterogorgia elisabethae collected in San Andrés island, Colombia has resulted in the discovery of a novel metabolite, elisapterosin F (1). The tangled molecular structure of 1, which was elucidated after extensive spectroscopic data interpretation, possesses hydrophilic and hydrophobic groups located on two opposite faces, rather than at two ends as in the more conventional head/tail amphiphiles. PMID:20161151

  15. Carboxymethyl chitosan-graft-phosphatidylethanolamine : amphiphilic matrices for controlled drug delivery

    OpenAIRE

    Prabaharan, M.; Reis, R. L.; Mano, J. F.

    2007-01-01

    Modified carboxymethyl chitosan (CMC) containing phosphatidylethanolamine (PEA) groups were synthesized by a 1- ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC)-mediated coupling reaction. The structure of the modified CMC exhibiting an amphiphilic character was analysed by FT-IR and 1H NMR. CMC-g-PEA beads were prepared with sodium tripolyphosphate (TPP) by ionic-crosslinking. The beads sizes were in range from 800 to 1200 lm and encapsulation efficiencies of drug were more than...

  16. ANIONIC SYNTHESIS OF A "CLICKABLE" MIDDLE-CHAIN AZIDEFUNCTIONALIZED POLYSTYRENE AND ITS APPLICATION IN SHAPE AMPHIPHILES

    Institute of Scientific and Technical Information of China (English)

    Kan Yue; Jinlin He; Chang Liu; Mingjun Huang; Xue-Hui Dong; Kai Guo; Peihong Ni

    2013-01-01

    "Click chemistry" is,by definition,a general functionalization methodology (GFM) and its marriage with living anionic polymerization is particularly powerful in precise macromolecular synthesis.This paper reports the synthesis of a "clickable" middle-chain azide-functionalized polystyrene (mPS-N3) by anionic polymerization and its application in the preparation of novel shape amphiphiles based on polyhedral oligomeric silsesquioxane (POSS).The mPS-N3 was synthesized by coupling living poly(styryl)lithium chains (PSLi) with 3-chloropropylmethyldichlorosilane and subsequent nucleophilic substitution of the chloro group in the presence of sodium azide.Excess PSLi was end-capped with ethylene oxide to facilitate its removal by flash chromatography.The mPS-N3 was then derived into a giant lipid-like shape amphiphile in two steps following a sequential "click" strategy.The copper(I)-catalyzed azide-alkyne cycloaddition between mPS-N3 and alkyne-functionalized vinyl-substituted POSS derivative (VPOSS-alkyne) ensured quantitative ligation to give polystyrene with VPOSS tethered at the middle of the chain (mPS-VPOSS).The thiol-ene reaction with 1-thioglycerol transforms the vinyl groups on the POSS periphery to hydroxyls,resulting in an amphiphilic shape amphiphile,mPS-DPOSS.This synthetic approach is highly efficient and modular.It demonstrates the "click" philosophy of facile complex molecule construction from a library of simple building blocks and also suggests that mPS-N3 can be used as a versatile "clickable" motif in polymer science for the precise synthesis of complex macromolecules.

  17. A comparative study of the physicochemical properties of perfluorinated and hydrogenated amphiphiles.

    Science.gov (United States)

    Blanco, Elena; González-Pérez, Alfredo; Ruso, Juan M; Pedrido, Rosa; Prieto, Gerardo; Sarmiento, Félix

    2005-08-01

    In this work we studied and compared the physicochemical properties of perfluorinated (sodium perfluoroheptanoate, C7FONa, and perfluorooctanoate, C8FONa) and hydrogenated (sodium octanoate, C8HONa, decanoate, C10HONa, and dodecanoate, C12HONa) amphiphiles. First, we determined their Krafft points to study the solubility and appropriate temperature range of micellization of these compounds. The critical micelle concentration (cmc) and ionization degree of micellization (beta) as a function of temperature (T) were estimated from conductivity data. Plots of cmc vs T appear to follow the typical U-shaped curve with a minimum T(min). The results show that the surfactants with CF2/CH2 ratio of 1.5 between alkyl chains (C12HONa-C8FONa and C10HONa-C7FONa) have nearly the same minimum value for cmc against temperature. The comparison between the cmc of hydrogenated amphiphiles and the corresponding perfluorinated amphiphiles must be done at this point. Thermodynamic functions of micellization were obtained by applying different theoretical models and choosing the one that best fit our experimental data. Although perfluorinated and hydrogenated amphiphiles present similar thermodynamic behavior, we have found a variation of 1.3 to 1.7 in the CF2/CH2 ratio, which did not remain constant with temperature. In the second part of this study the apparent molar volumes and adiabatic compressibilities were determined from density and ultrasound velocity measurements. Apparent molar volumes at infinite dilution presented the ratio 1.5 between alkyl chains again. However, apparent molar volumes upon micellization for sodium perfluoroheptanoate indicated a different aggregation pattern.

  18. Micellar interactions in water-AOT based droplet microemulsions containing hydrophilic and amphiphilic polymers

    Science.gov (United States)

    Appel, Markus; Spehr, Tinka Luise; Wipf, Robert; Moers, Christian; Frey, Holger; Stühn, Bernd

    2013-11-01

    We investigate the influence of addition of hydrophilic and amphiphilic polymer on percolation behavior and micellar interactions in AOT-based water-in-oil droplet microemulsions. We focus on two series of samples having constant molar water to surfactant ratio W = 20 and constant droplet volume fraction Φ = 30%, respectively. From dielectric spectroscopy experiments, we extract the bending rigidity of the surfactant shell by percolation temperature measurements. Depending on droplet size, we find stabilization and destabilization of the surfactant shell upon addition of hydrophilic poly(ethylene glycol) (PEG) (Mn = 3100 g mol-1) and amphiphilic poly(styrene)-b-poly(ethylene glycol) copolymer with comparable length of the hydrophilic block. Complementary small angle X-ray scattering experiments corroborate the finding of stabilization for smaller droplets and destabilization of larger droplets. Subsequent analysis of dielectric spectra enables us to extract detailed information about micellar interactions and clustering by evaluating the dielectric high frequency shell relaxation. We interpret the observed results as a possible modification of the inter-droplet charge transfer efficiency by addition of PEG polymer, while the amphiphilic polymer shows a comparable, but dampened effect.

  19. Ultrasound-driven secondary self-assembly of amphiphilic β-cyclodextrin dimers.

    Science.gov (United States)

    Zhang, Hai-tao; Fan, Xiao-dong; Tian, Wei; Suo, Rong-tian; Yang, Zhen; Bai, Yang; Zhang, Wan-bin

    2015-03-23

    The controlled secondary self-assembly of amphiphilic molecules in solution is theoretically and practically significant in amphiphilic molecular applications. An amphiphilic β-cyclodextrin (β-CD) dimer, namely LA-(CD)2 , has been synthesized, wherein one lithocholic acid (LA) unit is hydrophobic and two β-CD units are hydrophilic. In an aqueous solution at room temperature, LA-(CD)2 self-assembles into spherical micelles without ultrasonication. The primary micelles dissociates and then secondarily form self-assemblies with branched structures under ultrasonication. The branched aggregates revert to primary micelles at high temperature. The ultrasound-driven secondary self-assembly is confirmed by transmission electron microscopy, dynamic light scattering, (1) H NMR spectroscopy, and Cu(2+) -responsive experiments. Furthermore, 2D NOESY NMR and UV/Vis spectroscopy results indicate that the formation of the primary micelles is driven by hydrophilic-hydrophobic interactions, whereas host-guest interactions promote the formation of the secondary assemblies. Additionally, ultrasonication is shown to be able to effectively destroy the primary hydrophilic-hydrophobic balances while enhancing the host-guest interaction between the LA and β-CD moieties at room temperature. PMID:25581876

  20. 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.

  1. Bioinspired amphiphilic phosphate block copolymers as non-fluoride materials to prevent dental erosion.

    Science.gov (United States)

    Lei, Yanda; Wang, Tongxin; Mitchell, James W; Zaidel, Lynette; Qiu, Jianhong; Kilpatrick-Liverman, LaTonya

    2014-01-01

    Inspired by the fact that certain natural proteins, e.g. casein phosphopeptide or amelogenin, are able to prevent tooth erosion (mineral loss) and to enhance tooth remineralization, a synthetic amphiphilic diblock copolymer, containing a hydrophilic methacryloyloxyethyl phosphate block (MOEP) and a hydrophobic methyl methacrylate block (MMA), was designed as a novel non-fluoride agent to prevent tooth erosion under acidic conditions. The structure of the polymer, synthesized by reversible addition-fragment transfer (RAFT) polymerization, was confirmed by gel permeation chromatography (GPC), Fourier transform infrared spectroscopy (FTIR), and nuclear magnetic resonance spectroscopy (NMR). While the hydrophilic PMOEP block within the amphiphilic block copolymer strongly binds to the enamel surface, the PMMA block forms a hydrophobic shell to prevent acid attack on tooth enamel, thus preventing/reducing acid erosion. The polymer treatment not only effectively decreased the mineral loss of hydroxyapatite (HAP) by 36-46% compared to the untreated control, but also protected the surface morphology of the enamel specimen following exposure to acid. Additionally, experimental results confirmed that low pH values and high polymer concentrations facilitate polymer binding. Thus, the preliminary data suggests that this new amphiphilic diblock copolymer has the potential to be used as a non-fluoride ingredient for mouth-rinse or toothpaste to prevent/reduce tooth erosion. PMID:25419457

  2. New Amphiphilic Polypyridyl Ruthenium(Ⅱ) Sensitizer and Its Application in Dye-Sensitized Solar Cells

    Institute of Scientific and Technical Information of China (English)

    KONG Fan-Tai; DAI Song-Yuan; WANG Kong-Jia

    2007-01-01

    Amphiphilic polypyridyl ruthenium(Ⅱ) complex cis-di(isothiocyanato)(4,4'-di-tert-butyl-2,2'-bipyridyl)(4,4'-dicarboxy-2,2'-bipyridyl)ruthenium(Ⅱ) (K005) has been synthesized and characterized by cyclic voltammetry, 1H NMR, UV-Vis, and FT-IR spectroscopies. The sensitizer sensitizes TiO2 over a notably broad spectral range due to its intense metal-to-ligand charge-transfer (MLCT) bands at 537 and 418 nm. The photophysical and photochemical studies of K005 were contrasted with those of cis-Ru(dcbpy)2(NCS)2, known as the N3 dye, and the amphiphilic ruthenium(Ⅱ) dye Z907. A reversible couple at E1/2=0.725 V vs. saturated calomel electrode (SCE) with a separation of 0.08 V between the anodic and cathodic peaks, was observed due to the RuⅡ/Ⅲ couple by cyclic voltammetry.Furthermore, this amphiphilic ruthenium complex was successfully used as sensitizers for dye-sensitized solar cells with the efficiency of 3.72% at the 100 mW·cm-2 irradiance of air mass 1.5 simulated sunlight without optimization of TiO2 films and the electrolyte.

  3. CONTROLLED SYNTHESIS OF AMPHIPHILIC BLOCK POLYMERS HAVING GLUCOSE RESIDUES AND THEIR STRUCTURE FORMATION

    Institute of Scientific and Technical Information of China (English)

    Takeaki Miyamoto; Masahiko Minoda; Yoshinobu Tsujii

    1999-01-01

    Vinyl ether (VE)-based amphiphilic block copolymers with D-glucose residues as hydrophilic pendants were synthesized by CH3CH(OiBu)Cl/ZnI2-initiated sequential living cationic copolymerization of 3-O-(vinyloxy)ethyl-1, 2:5, 6-di-O-isopropylidene-D-glucofuranose (IGVE) and isobutyl VE (IBVE) and subsequent deprotection. The precursor block copolymers had a narrow molecular weight distribution(Mw/Mn~1.1) and a controlled segmental composition. The solubility characteristics of the amphiphilic copolymer depended strongly on composition. Their solvent-cast thin films were examined, under a transmission electron microscope, and could be seen to exhibit various microphase-separated surface morphologies such as spheres, cylinders, and lamellae, depending on composition. The amphiphilic copolymers with the appropriate segmental composition were found to form a stable monolayer at the airwater interface, which was successfully transferred onto a substrate by the Langmuir-Blodgett (LB)technique. The layered structure of the built-up LB films was controlled by blending the homopolymer.

  4. A Phytic Acid Induced Super-Amphiphilic Multifunctional 3D Graphene-Based Foam.

    Science.gov (United States)

    Song, Xinhong; Chen, Yiying; Rong, Mingcong; Xie, Zhaoxiong; Zhao, Tingting; Wang, Yiru; Chen, Xi; Wolfbeis, Otto S

    2016-03-14

    Surfaces with super-amphiphilicity have attracted tremendous interest for fundamental and applied research owing to their special affinity to both oil and water. It is generally believed that 3D graphenes are monoliths with strongly hydrophobic surfaces. Herein, we demonstrate the preparation of a 3D super-amphiphilic (that is, highly hydrophilic and oleophilic) graphene-based assembly in a single-step using phytic acid acting as both a gelator and as a dopant. The product shows both hydrophilic and oleophilic intelligence, and this overcomes the drawbacks of presently known hydrophobic 3D graphene assemblies. It can absorb water and oils alike. The utility of the new material was demonstrated by designing a heterogeneous catalytic system through incorporation of a zeolite into its amphiphilic 3D scaffold. The resulting bulk network was shown to enable efficient epoxidation of alkenes without prior addition of a co-solvent or stirring. This catalyst also can be recovered and re-used, thereby providing a clean catalytic process with simplified work-up. PMID:26890034

  5. The search for new amphiphiles: synthesis of a modular, high-throughput library

    Directory of Open Access Journals (Sweden)

    George C. Feast

    2014-07-01

    Full Text Available Amphiphilic compounds are used in a variety of applications due to their lyotropic liquid-crystalline phase formation, however only a limited number of compounds, in a potentially limitless field, are currently in use. A library of organic amphiphilic compounds was synthesised consisting of glucose, galactose, lactose, xylose and mannose head groups and double and triple-chain hydrophobic tails. A modular, high-throughput approach was developed, whereby head and tail components were conjugated using the copper-catalysed azide–alkyne cycloaddition (CuAAC reaction. The tails were synthesised from two core alkyne-tethered intermediates, which were subsequently functionalised with hydrocarbon chains varying in length and degree of unsaturation and branching, while the five sugar head groups were selected with ranging substitution patterns and anomeric linkages. A library of 80 amphiphiles was subsequently produced, using a 24-vial array, with the majority formed in very good to excellent yields. A preliminary assessment of the liquid-crystalline phase behaviour is also presented.

  6. Hierarchy of Specific Lipid-Peptide Interactions Produces the Activity of Cell-penetrating and Cell-permeating Peptides

    Science.gov (United States)

    Davis, Matthew; Parente, Daniel; Gordon, Vernita; Mishra, Abhijit; Schmidt, Nathan; Yang, Lihua; Coridan, Robert; Som, Abhigyan; Tew, Gregory; Wong, Gerard

    2008-03-01

    Protein transduction domains can cross cell membranes with high efficiency, even when carrying a variety of cargos, and thus has strong biotechnological potential. The molecular mechanism of entry, however, is not well understood. We use small-angle x-ray scattering (SAXS) and confocal microscopy to systematically study the interaction of the TAT and ANTP PTD with model membranes of variable composition. Their membrane transduction activity requires the presence of both PE and PS lipids in the membrane. Antimicrobial peptides (AMP's) are cationic amphiphiles that comprise a key component of innate immunity. Synthetic analogs of AMP's, such as the family of phenylene ethynylene antimicrobial oligomers (AMO's), recently demonstrated broad-spectrum antimicrobial activity, but the underlying molecular mechanism is unknown. PE lipid greatly enhances permeating activity of AMO in these membranes, showing the importance of specific lipid composition for the activity of cell-permeating peptides. Since bacterial cell membranes are richer in PE lipids than are eukaryotic cell membranes, this may indicate a mechanism for antimicrobial specificity.

  7. Information-driven modeling of protein-peptide complexes.

    Science.gov (United States)

    Trellet, Mikael; Melquiond, Adrien S J; Bonvin, Alexandre M J J

    2015-01-01

    Despite their biological importance in many regulatory processes, protein-peptide recognition mechanisms are difficult to study experimentally at the structural level because of the inherent flexibility of peptides and the often transient interactions on which they rely. Complementary methods like biomolecular docking are therefore required. The prediction of the three-dimensional structure of protein-peptide complexes raises unique challenges for computational algorithms, as exemplified by the recent introduction of protein-peptide targets in the blind international experiment CAPRI (Critical Assessment of PRedicted Interactions). Conventional protein-protein docking approaches are often struggling with the high flexibility of peptides whose short sizes impede protocols and scoring functions developed for larger interfaces. On the other side, protein-small ligand docking methods are unable to cope with the larger number of degrees of freedom in peptides compared to small molecules and the typically reduced available information to define the binding site. In this chapter, we describe a protocol to model protein-peptide complexes using the HADDOCK web server, working through a test case to illustrate every steps. The flexibility challenge that peptides represent is dealt with by combining elements of conformational selection and induced fit molecular recognition theories. PMID:25555727

  8. PNA Peptide chimerae

    DEFF Research Database (Denmark)

    Koch, T.; Næsby, M.; Wittung, P.;

    1995-01-01

    Radioactive labelling of PNA has been performed try linking a peptide segment to the PNA which is substrate for protein kinase A. The enzymatic phosphorylation proceeds in almost quantitative yields....

  9. Computational Design of Peptide Ligands for Ochratoxin A

    Directory of Open Access Journals (Sweden)

    Meike Heurich

    2013-06-01

    Full Text Available In this paper, we describe a peptide library designed by computational modelling and the selection of two peptide sequences showing affinity towards the mycotoxin, ochratoxin A (OTA. A virtual library of 20 natural amino acids was used as building blocks to design a short peptide library against ochratoxin A template using the de novo design program, LeapFrog, and the dynamic modelling software, FlexiDock. Peptide sequences were ranked according to calculated binding scores in their capacity to bind to ochratoxin A. Two high scoring peptides with the sequences N'-Cys-Ser-Ile-Val-Glu-Asp-Gly-Lys-C' (octapeptide and N'-Gly-Pro-Ala-Gly-Ile-Asp-Gly-Pro-Ala-Gly-Ile-Arg-Cys-C' (13-mer were selected for synthesis from the resulting database. These synthesized peptides were characterized using a microtitre plate-based binding assay and a surface plasmon resonance biosensor (Biacore 3000. The binding assay confirmed that both de novo designed peptides did bind to ochratoxin A in vitro. SPR analysis confirmed that the peptides bind to ochratoxin A, with calculated KD values of ~15.7 μM (13-mer and ~11.8 μM (octamer. The affinity of the peptides corresponds well with the molecular modelling results, as the 13-mer peptide affinity is about 1.3-times weaker than the octapeptide; this is in accordance with the binding energy values modelled by FlexiDock. This work illustrates the potential of using computational modelling to design a peptide sequence that exhibits in vitro binding affinity for a small molecular weight toxin.

  10. 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

  11. Introduction to Peptide Synthesis

    OpenAIRE

    Stawikowski, Maciej; Fields, Gregg B.

    2002-01-01

    A number of synthetic peptides are significant commercial or pharmaceutical products, ranging from the dipeptide sugar-substitute aspartame to clinically used hormones, such as oxytocin, adrenocorticotropic hormone, and calcitonin. This unit provides an overview of the field of synthetic peptides and proteins. It discusses selecting the solid support and common coupling reagents. Additional information is provided regarding common side reactions and synthesizing modified residues.

  12. Selection of a peptide mimicking neutralization epitope of hepatitis E virus with phage peptide display technology

    Institute of Scientific and Technical Information of China (English)

    Ying Gu; Jun Zhang; Ying-Bing Wang; Shao-Wei Li; Hai-Jie Yang; Wen-Xin Luo; Ning-Shao Xia

    2004-01-01

    AIM: To select the peptide mimicking the neutralization epitope of hepatitis E virus which bound to non-type-specific and conformational monoclonal antibodies (mAbs) 8C11 and 8H3 fromed 7-peptide phage display library, and expressed the peptide recombinant with HBcAg in E.coli, and to observe whether the recombinant HBcAg could still form virus like particle (VLP) and to test the activation of the recombinant polyprotein and chemo-synthesized peptide that was selected by mAb 8H3.METHODS: 8C11 and 8H3 were used to screen for binding peptides through a 7-peptide phage display library. After 4rounds of panning, monoclonal phages were selected and sequenced. The obtained dominant peptide coding sequences was then synthesized and inserted into amino acid 78 to 83 of hepatitis B core antigen (HBcAg), and then expressed in E. coli. Activity of the recombinant proteins was detected by Western blotting, VLPs of the recombinant polyproteins were tested by transmission electron microscopy and binding activity of the chemo-synthesized peptide was confirmed by BIAcore biosensor.RESULTS: Twenty-one positive monoclonal phages (10for 8CL1, and 11 for 8H3) were selected and the inserted fragments were sequenced. The DNA sequence coding for the obtained dominant peptides 8C11 (N′-His-Pro-Thr-LeuLeu-Arg-Ile-C′, named 8C11A) and 8H3 (N′-Ser-Ile-LeuPro- Tyr-Pro-Tyr-C′, named 8H3A) were then synthesized and cloned to the HBcAg vector, then expressed in E. coli.The recombinant proteins aggregated into homodimer or polymer on SDS-PAGE, and could bind to mAb 8C11 and 8H3 in Western blotting. At the same time, the recombinant polyprotein could form virus like particles (VLPs), which could be visualized on electron micrograph. The dominant peptide 8H3A selected by mAb 8H3 was further chemosynthesized, and its binding to mAb 8H3 could be detected by BIAcore biosensor.CONCLUSION: These results implicate that conformational neutralizing epitope can be partially modeled by a short

  13. Aerosolized Medications for Gene and Peptide Therapy.

    Science.gov (United States)

    Laube, Beth L

    2015-06-01

    Inhalation therapy has matured to include drugs that: (1) deliver nucleic acids that either lead to the restoration of a gene construct or protein coding sequence in a population of cells or suppress or disrupt production of an abnormal gene product (gene therapy); (2) deliver peptides that target lung diseases such as asthma, sarcoidosis, pulmonary hypertension, and cystic fibrosis; and (3) deliver peptides to treat diseases outside the lung whose target is the systemic circulation (systemic drug delivery). These newer applications for aerosol therapy are the focus of this paper, and I discuss the status of each and the challenges that remain to their successful development. Drugs that are highlighted include: small interfering ribonucleic acid to treat lung cancer and Mycobacterium tuberculosis; vectors carrying the normal alpha-1 antitrypsin gene to treat alpha-1 antitrypsin deficiency; vectors carrying the normal cystic fibrosis transmembrane conductance regulator gene to treat cystic fibrosis; vasoactive intestinal peptide to treat asthma, pulmonary hypertension, and sarcoidosis; glutathione to treat cystic fibrosis; granulocyte-macrophage colony-stimulating factor to treat pulmonary alveolar proteinosis; calcitonin for postmenopausal osteoporosis; and insulin to treat diabetes. The success of these new aerosol applications will depend on many factors, such as: (1) developing gene therapy formulations that are safe for acute and chronic administrations to the lung, (2) improving the delivery of the genetic material beyond the airway mucus barrier and cell membrane and transferring the material to the cell cytoplasm or the cell nucleus, (3) developing aerosol devices that efficiently deliver genetic material and peptides to their lung targets over a short period of time, (4) developing devices that increase aerosol delivery to the lungs of infants, (5) optimizing the bioavailability of systemically delivered peptides, and (6) developing peptide formulations for

  14. Albumin pre-coating enhances intracellular siRNA delivery of multifunctional amphiphile/siRNA nanoparticles

    Directory of Open Access Journals (Sweden)

    Kummitha CM

    2012-10-01

    Full Text Available China M Kummitha, Anthony S Malamas, Zheng-Rong LuDepartment of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USAAbstract: Nonspecific association of serum molecules with short-interfering RNA (siRNA nanoparticles can change their physiochemical characteristics, and results in reduced cellular uptake in the target tissue during the systemic siRNA delivery process. Serum albumin is the most abundant protein in the body and has been used to modify the surface of nanoparticles, to inhibit association of other serum molecules. Here, we hypothesized that surface modification of lipid-based nanoparticular siRNA delivery systems with albumin could prevent their interaction with serum proteins, and improve intracellular uptake. In this study, we investigated the influence of albumin on the stability and intracellular siRNA delivery of the targeted siRNA nanoparticles of a polymerizable and pH-sensitive multifunctional surfactant N-(1-aminoethyliminobis[N-(oleoylcysteinylhistinyl-1-aminoethylpropionamide] (EHCO in serum. Serum resulted in a significant increase in the size of targeted EHCO/siRNA nanoparticles and inhibited cellular uptake of the nanoparticles. Coating of targeted EHCO/siRNA nanoparticles with bovine serum albumin at 9.4 µM prior to cell transfection improved cellular uptake and gene silencing efficacy of EHCO/siRNA targeted nanoparticles in serum-containing media, as compared with the uncoated nanoparticles. At a proper concentration, albumin has the potential to minimize interactions of serum proteins with siRNA nanoparticles for effective systemic in vivo siRNA delivery.Keywords: multifunctional, lipid nanoparticles, RNA interference, pH-sensitive amphiphile, siRNA

  15. Entropic (de)stabilization of surface-bound peptides conjugated with polymers

    Science.gov (United States)

    Carmichael, Scott P.; Shell, M. Scott

    2015-12-01

    In many emerging biotechnologies, functional proteins must maintain their native structures on or near interfaces (e.g., tethered peptide arrays, protein coated nanoparticles, and amphiphilic peptide micelles). Because the presence of a surface is known to dramatically alter the thermostability of tethered proteins, strategies to stabilize surface-bound proteins are highly sought. Here, we show that polymer conjugation allows for significant control over the secondary structure and thermostability of a model surface-tethered peptide. We use molecular dynamics simulations to examine the folding behavior of a coarse-grained helical peptide that is conjugated to polymers of various lengths and at various conjugation sites. These polymer variations reveal surprisingly diverse behavior, with some stabilizing and some destabilizing the native helical fold. We show that ideal-chain polymer entropies explain these varied effects and can quantitatively predict shifts in folding temperature. We then develop a generic theoretical model, based on ideal-chain entropies, that predicts critical lengths for conjugated polymers to effect changes in the folding of a surface-bound protein. These results may inform new design strategies for the stabilization of surface-associated proteins important for a range technological applications.

  16. 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).

  17. Entropic (de)stabilization of surface-bound peptides conjugated with polymers.

    Science.gov (United States)

    Carmichael, Scott P; Shell, M Scott

    2015-12-28

    In many emerging biotechnologies, functional proteins must maintain their native structures on or near interfaces (e.g., tethered peptide arrays, protein coated nanoparticles, and amphiphilic peptide micelles). Because the presence of a surface is known to dramatically alter the thermostability of tethered proteins, strategies to stabilize surface-bound proteins are highly sought. Here, we show that polymer conjugation allows for significant control over the secondary structure and thermostability of a model surface-tethered peptide. We use molecular dynamics simulations to examine the folding behavior of a coarse-grained helical peptide that is conjugated to polymers of various lengths and at various conjugation sites. These polymer variations reveal surprisingly diverse behavior, with some stabilizing and some destabilizing the native helical fold. We show that ideal-chain polymer entropies explain these varied effects and can quantitatively predict shifts in folding temperature. We then develop a generic theoretical model, based on ideal-chain entropies, that predicts critical lengths for conjugated polymers to effect changes in the folding of a surface-bound protein. These results may inform new design strategies for the stabilization of surface-associated proteins important for a range technological applications.

  18. Structure, orientation, and surface interaction of Alzheimer amyloid-β peptides on the graphite.

    Science.gov (United States)

    Yu, Xiang; Wang, Qiuming; Lin, Yinan; Zhao, Jun; Zhao, Chao; Zheng, Jie

    2012-04-24

    The misfolding and aggregation of amyloid-β (Aβ) peptides into amyloid fibrils in solution and on the cell membrane has been linked to the pathogenesis of Alzheimer's disease. Although it is well-known that the presence of different surfaces can accelerate the aggregation of Aβ peptides into fibrils, surface-induced conformation, orientation, aggregation, and adsorption of Aβ peptides have not been well understood at the atomic level. Here, we perform all-atom explicit-water molecular dynamics (MD) simulations to study the orientation change, conformational dynamics, surface interaction of small Aβ aggregates with different sizes (monomer to tetramer), and conformations (α-helix and β-hairpin) upon adsorption on the graphite surface, in comparison with Aβ structures in bulk solution. Simulation results show that hydrophobic graphite induces the quick adsorption of Aβ peptides regardless of their initial conformations and sizes. Upon the adsorption, Aβ prefers to adopt random structure for monomers and to remain β-rich-structure for small oligomers, but not helical structures. More importantly, due to the amphiphilic sequence of Aβ and the hydrophobic nature of graphite, hydrophobic C-terminal residues of higher-order Aβ oligomers appear to have preferential interactions with the graphite surface for facilitating Aβ fibril formation and fibril growth. In combination of atomic force microscopy (AFM) images and MD simulation results, a postulated mechanism is proposed to describe the structure and kinetics of Aβ aggregation from aqueous solution to the graphite surface, providing parallel insights into Aβ aggregation on biological cell membranes.

  19. Identification of binding peptides of the ADAM15 disintegrin domain using phage display

    Indian Academy of Sciences (India)

    Jing Wu; Min-Chen Wu; Lian-Fen Zhang; Jian-Yong Lei; Lei Feng; Jian Jin

    2009-06-01

    ADAM15 plays an important role in tumour development by interacting with integrins. In this study, we investigated the target peptides of the ADAM15 disintegrin domain. First, we successfully produced the recombinant human ADAM15 disintegrin domain (RADD) that could inhibit melanoma cell adhesion by using Escherichia coli. Second, four specific binding peptides (peptides A, B, C, and D) were selected using a phage display 12-mer peptide library. The screening protocol involved 4 rounds of positive panning on RADD and 2 rounds of subtractive selection with streptavidin. By using the BLAST software and a relevant protein database, integrin v3 was found to be homologous to peptide A. Synthetic peptide A had a highly inhibitory effect on RADD–integrin v3 binding. The results demonstrate the potential application of short peptides for disrupting high-affinity ADAM–integrin interactions.

  20. Biomimetic peptide-based models of [FeFe]-hydrogenases: utilization of phosphine-containing peptides.

    Science.gov (United States)

    Roy, Souvik; Nguyen, Thuy-Ai D; Gan, Lu; Jones, Anne K

    2015-09-01

    Two synthetic strategies for incorporating diiron analogues of [FeFe]-hydrogenases into short peptides via phosphine functional groups are described. First, utilizing the amine side chain of lysine as an anchor, phosphine carboxylic acids can be coupled via amide formation to resin-bound peptides. Second, artificial, phosphine-containing amino acids can be directly incorporated into peptides via solution phase peptide synthesis. The second approach is demonstrated using three amino acids each with a different phosphine substituent (diphenyl, diisopropyl, and diethyl phosphine). In total, five distinct monophosphine-substituted, diiron model complexes were prepared by reaction of the phosphine-peptides with diiron hexacarbonyl precursors, either (μ-pdt)Fe2(CO)6 or (μ-bdt)Fe2(CO)6 (pdt = propane-1,3-dithiolate, bdt = benzene-1,2-dithiolate). Formation of the complexes was confirmed by UV/Vis, FTIR and (31)P NMR spectroscopy. Electrocatalysis by these complexes is reported in the presence of acetic acid in mixed aqueous-organic solutions. Addition of water results in enhancement of the catalytic rates.

  1. SH3 domain-peptide binding energy calculations based on structural ensemble and multiple peptide templates.

    Directory of Open Access Journals (Sweden)

    Seungpyo Hong

    Full Text Available SH3 domains mediate signal transduction by recognizing short peptides. Understanding of the driving forces in peptide recognitions will help us to predict the binding specificity of the domain-peptide recognition and to understand the molecular interaction networks of cells. However, accurate calculation of the binding energy is a tough challenge. In this study, we propose three ideas for improving our ability to predict the binding energy between SH3 domains and peptides: (1 utilizing the structural ensembles sampled from a molecular dynamics simulation trajectory, (2 utilizing multiple peptide templates, and (3 optimizing the sequence-structure mapping. We tested these three ideas on ten previously studied SH3 domains for which SPOT analysis data were available. The results indicate that calculating binding energy using the structural ensemble was most effective, clearly increasing the prediction accuracy, while the second and third ideas tended to give better binding energy predictions. We applied our method to the five SH3 targets in DREAM4 Challenge and selected the best performing method.

  2. Sequence-selective DNA binding with cell-permeable oligoguanidinium-peptide conjugates.

    Science.gov (United States)

    Mosquera, Jesús; Sánchez, Mateo I; Valero, Julián; de Mendoza, Javier; Vázquez, M Eugenio; Mascareñas, José L

    2015-03-21

    Conjugation of a short peptide fragment from a bZIP protein to an oligoguanidinium tail results in a DNA-binding miniprotein that selectively interacts with composite sequences containing the peptide-binding site next to an A/T-rich tract. In addition to stabilizing the complex with the target DNA, the oligoguanidinium unit also endows the conjugate with cell internalization properties.

  3. Dysferlin-peptides reallocate mutated dysferlin thereby restoring function.

    Directory of Open Access Journals (Sweden)

    Verena Schoewel

    Full Text Available Mutations in the dysferlin gene cause the most frequent adult-onset limb girdle muscular dystrophy, LGMD2B. There is no therapy. Dysferlin is a membrane protein comprised of seven, beta-sheet enriched, C2 domains and is involved in Ca(2+dependent sarcolemmal repair after minute wounding. On the protein level, point mutations in DYSF lead to misfolding, aggregation within the endoplasmic reticulum, and amyloidogenesis. We aimed to restore functionality by relocating mutant dysferlin. Therefore, we designed short peptides derived from dysferlin itself and labeled them to the cell penetrating peptide TAT. By tracking fluorescently labeled short peptides we show that these dysferlin-peptides localize in the endoplasmic reticulum. There, they are capable of reducing unfolded protein response stress. We demonstrate that the mutant dysferlin regains function in membrane repair in primary human myotubes derived from patients' myoblasts by the laser wounding assay and a novel technique to investigate membrane repair: the interventional atomic force microscopy. Mutant dysferlin abuts to the sarcolemma after peptide treatment. The peptide-mediated approach has not been taken before in the field of muscular dystrophies. Our results could redirect treatment efforts for this condition.

  4. Dysferlin-peptides reallocate mutated dysferlin thereby restoring function.

    Science.gov (United States)

    Schoewel, Verena; Marg, Andreas; Kunz, Severine; Overkamp, Tim; Carrazedo, Romy Siegert; Zacharias, Ute; Daniel, Peter T; Spuler, Simone

    2012-01-01

    Mutations in the dysferlin gene cause the most frequent adult-onset limb girdle muscular dystrophy, LGMD2B. There is no therapy. Dysferlin is a membrane protein comprised of seven, beta-sheet enriched, C2 domains and is involved in Ca(2+)dependent sarcolemmal repair after minute wounding. On the protein level, point mutations in DYSF lead to misfolding, aggregation within the endoplasmic reticulum, and amyloidogenesis. We aimed to restore functionality by relocating mutant dysferlin. Therefore, we designed short peptides derived from dysferlin itself and labeled them to the cell penetrating peptide TAT. By tracking fluorescently labeled short peptides we show that these dysferlin-peptides localize in the endoplasmic reticulum. There, they are capable of reducing unfolded protein response stress. We demonstrate that the mutant dysferlin regains function in membrane repair in primary human myotubes derived from patients' myoblasts by the laser wounding assay and a novel technique to investigate membrane repair: the interventional atomic force microscopy. Mutant dysferlin abuts to the sarcolemma after peptide treatment. The peptide-mediated approach has not been taken before in the field of muscular dystrophies. Our results could redirect treatment efforts for this condition. PMID:23185377

  5. Antimicrobial Peptides from Plants

    Science.gov (United States)

    Tam, James P.; Wang, Shujing; Wong, Ka H.; Tan, Wei Liang

    2015-01-01

    Plant antimicrobial peptides (AMPs) have evolved differently from AMPs from other life forms. They are generally rich in cysteine residues which form multiple disulfides. In turn, the disulfides cross-braced plant AMPs as cystine-rich peptides to confer them with extraordinary high chemical, thermal and proteolytic stability. The cystine-rich or commonly known as cysteine-rich peptides (CRPs) of plant AMPs are classified into families based on their sequence similarity, cysteine motifs that determine their distinctive disulfide bond patterns and tertiary structure fold. Cystine-rich plant AMP families include thionins, defensins, hevein-like peptides, knottin-type peptides (linear and cyclic), lipid transfer proteins, α-hairpinin and snakins family. In addition, there are AMPs which are rich in other amino acids. The ability of plant AMPs to organize into specific families with conserved structural folds that enable sequence variation of non-Cys residues encased in the same scaffold within a particular family to play multiple functions. Furthermore, the ability of plant AMPs to tolerate hypervariable sequences using a conserved scaffold provides diversity to recognize different targets by varying the sequence of the non-cysteine residues. These properties bode well for developing plant AMPs as potential therapeutics and for protection of crops through transgenic methods. This review provides an overview of the major families of plant AMPs, including their structures, functions, and putative mechanisms. PMID:26580629

  6. Antimicrobial Peptides from Plants

    Directory of Open Access Journals (Sweden)

    James P. Tam

    2015-11-01

    Full Text Available Plant antimicrobial peptides (AMPs have evolved differently from AMPs from other life forms. They are generally rich in cysteine residues which form multiple disulfides. In turn, the disulfides cross-braced plant AMPs as cystine-rich peptides to confer them with extraordinary high chemical, thermal and proteolytic stability. The cystine-rich or commonly known as cysteine-rich peptides (CRPs of plant AMPs are classified into families based on their sequence similarity, cysteine motifs that determine their distinctive disulfide bond patterns and tertiary structure fold. Cystine-rich plant AMP families include thionins, defensins, hevein-like peptides, knottin-type peptides (linear and cyclic, lipid transfer proteins, α-hairpinin and snakins family. In addition, there are AMPs which are rich in other amino acids. The ability of plant AMPs to organize into specific families with conserved structural folds that enable sequence variation of non-Cys residues encased in the same scaffold within a particular family to play multiple functions. Furthermore, the ability of plant AMPs to tolerate hypervariable sequences using a conserved scaffold provides diversity to recognize different targets by varying the sequence of the non-cysteine residues. These properties bode well for developing plant AMPs as potential therapeutics and for protection of crops through transgenic methods. This review provides an overview of the major families of plant AMPs, including their structures, functions, and putative mechanisms.

  7. Electron transfer in peptides.

    Science.gov (United States)

    Shah, Afzal; Adhikari, Bimalendu; Martic, Sanela; Munir, Azeema; Shahzad, Suniya; Ahmad, Khurshid; Kraatz, Heinz-Bernhard

    2015-02-21

    In this review, we discuss the factors that influence electron transfer in peptides. We summarize experimental results from solution and surface studies and highlight the ongoing debate on the mechanistic aspects of this fundamental reaction. Here, we provide a balanced approach that remains unbiased and does not favor one mechanistic view over another. Support for a putative hopping mechanism in which an electron transfers in a stepwise manner is contrasted with experimental results that support electron tunneling or even some form of ballistic transfer or a pathway transfer for an electron between donor and acceptor sites. In some cases, experimental evidence suggests that a change in the electron transfer mechanism occurs as a result of donor-acceptor separation. However, this common understanding of the switch between tunneling and hopping as a function of chain length is not sufficient for explaining electron transfer in peptides. Apart from chain length, several other factors such as the extent of the secondary structure, backbone conformation, dipole orientation, the presence of special amino acids, hydrogen bonding, and the dynamic properties of a peptide also influence the rate and mode of electron transfer in peptides. Electron transfer plays a key role in physical, chemical and biological systems, so its control is a fundamental task in bioelectrochemical systems, the design of peptide based sensors and molecular junctions. Therefore, this topic is at the heart of a number of biological and technological processes and thus remains of vital interest.

  8. Electromembrane extraction of peptides.

    Science.gov (United States)

    Balchen, Marte; Reubsaet, Léon; Pedersen-Bjergaard, Stig

    2008-06-20

    Rapid extraction of eight different peptides using electromembrane extraction (EME) was demonstrated for the first time. During an extraction time of 5 min, the model peptides migrated from a 500 microL aqueous acidic sample solution, through a thin supported liquid membrane (SLM) of an organic liquid sustained in the pores in the wall of a porous hollow fiber, and into a 25 microL aqueous acidic acceptor solution present inside the lumen of the hollow fiber. The driving force of the extraction was a 50 V potential sustained across the SLM, with the positive electrode in the sample and the negative electrode in the acceptor solution. The nature and the composition of the SLM were highly important for the EME process, and a mixture of 1-octanol and 15% di(2-ethylhexyl) phosphate was found to work properly. Using 1mM HCl as background electrolyte in the sample and 100 mM HCl in the acceptor solution, and agitation at 1050 rpm, enrichment up to 11 times was achieved. Recoveries were found to be dependent on the structure of the peptide, indicating that the polarity and the number of ionized groups were important parameters affecting the extraction efficiency. The experimental findings suggested that electromembrane extraction of peptides is possible and may be a valuable tool for future extraction of peptides. PMID:18479691

  9. TUMOR SELECTIVE DRUG DELIVERY BY NEUROTENSIN BRANCHED PEPTIDES

    Directory of Open Access Journals (Sweden)

    L. Depau

    2012-05-01

    Full Text Available Detection of new tumor-selective targets, which allow either cancer cell tracing or therapy, is a crucial issue in cancer research. Membrane receptors for endogenous peptides such as Neurotensin are over-expressed in many human cancers and could therefore be used as tumor-specific antigen, while peptide ligands might act as targeting agents. The development of peptides as drug has always been limited by their short half-life, due to degradation by peptidases and proteases. Chemical modification, which can stabilize the molecules, may modify peptide affinity or specificity. More- over, coupling of peptides to effector units for imaging or therapy, may interfere with biological activity. We demonstrated that peptide sequences, when synthesized in an oligo-branched form, be- come resistant to proteolysis and thank to their multimericity are more efficient than correspon- ding monomers in binding cellular antigens1. Moreover, the branched core allow coupling of effector units without affecting peptide activity. Drug-armed tetra-branched neurotensin peptides (NT4 were synthesized with different conjugation methods, resulting either in uncleavable adducts or drug-releasing molecules2-4. Recently we de- veloped DOPC liposomes filled with the cytotoxic drug Doxorubicin (Doxo and functionalized with NT4. Armed DOPC liposomes showed a clear advantage with respect to nude liposomes in drug internalization and their cytotoxicity is fourfold increased with respect to the same nude lipo- somes. Conjugation to NT4 switches drug internalization to a peptide-receptor mediated mechanism, which greatly increases drug selectivity and also might allow by-passing drug cell resistance. In vitro and in vivo results indicated that branched NT peptides are valuable tools for tumor selective targeting.

  10. 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.

  11. Self-assembly behavior of a linear-star supramolecular amphiphile based on host-guest complexation.

    Science.gov (United States)

    Wang, Juan; Wang, Xing; Yang, Fei; Shen, Hong; You, Yezi; Wu, Decheng

    2014-11-01

    A star polymer, β-cyclodextrin-poly(l-lactide) (β-CD-PLLA), and a linear polymer, azobenzene-poly(ethylene glycol) (Azo-PEG), could self-assemble into a supramolecular amphiphilic copolymer (β-CD-PLLA@Azo-PEG) based on the host-guest interaction between β-CD and azobenzene moieties. This linear-star supramolecular amphiphilic copolymer further self-assembled into a variety of morphologies, including sphere-like micelle, carambola-like micelle, naan-like micelle, shuttle-like lamellae, tube-like fiber, and random curled-up lamellae, by tuning the length of hydrophilic or hydrophobic chains. The variation of morphology was closely related to the topological structure and block ratio of the supramolecular amphiphiles. These self-assembly structures could disassemble upon an ultraviolet (UV) light irradiation. PMID:25310380

  12. Micro- and nanophase separations in hierarchical self-assembly of strongly amphiphilic block copolymer-based ionic supramolecules

    DEFF Research Database (Denmark)

    Ayoubi, Mehran Asad; Zhu, Kaizheng; Nyström, Bo;

    2013-01-01

    block), a class of ionic supramolecules are successfully synthesized whose molecular architecture consists of a poly(styrene) PS block (Linear block) covalently connected to a strongly amphiphilic comb-like block (AmphComb block), i.e. Linear-b-AmphComb. In the melt state, these ionic supramolecules can......By a selective complexation between different alkyltrimethylammonium amphiphiles (C8, C12 and C16) and three different diblock copolymer systems of poly(styrene)-b-poly(methacrylic acid) at various grafting densities X (X = number of alkyl chains per acidic group of the poly(methacrylic acid) PMAA...... supramolecules, based on complexation between a homopolymer of PMAA and the various alkyltrimethylammonium amphiphiles, were prepared, which nanophase separated into S (C8) or C (C12 and C16) domains....

  13. Therapeutic HIV Peptide Vaccine

    DEFF Research Database (Denmark)

    Fomsgaard, Anders

    2015-01-01

    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......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...... and hence adjuvants are included to enhance and direct the immune response. Although the vaccine has been tested in ART naïve individuals, we recommend future testing of the vaccine during (early started) ART that improves immune function and to select individuals likely to benefit. Peptides representing...

  14. 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. PMID:26724202

  15. 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.

  16. 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.

  17. Nonionic amphiphile nanoarchitectonics: self-assembly into micelles and lyotropic liquid crystals

    Science.gov (United States)

    Shrestha, Lok Kumar; Strzelczyk, Karolina Maria; Goswami Shrestha, Rekha; Ichikawa, Kotoko; Aramaki, Kenji; Hill, Jonathan P.; Ariga, Katsuhiko

    2015-05-01

    Amphiphiles, molecules that possess both hydrophilic and hydrophobic moieties, are architecturally simple molecules that can spontaneously self-assemble into complex hierarchical structures from lower to higher dimensions either in the bulk phase or at an interface. Recent developments in multifunctional nanostructure design using the advanced concept of nanoarchitectonics utilize this simple process of assembly. Amphiphilic self-assemblies involving lipids or proteins mimic the structure of biological systems, thus highlighting the necessity of a fundamental physical understanding of amphiphilic self-assembly towards a realization of the complex mechanisms operating in nature. Herein, we describe self-assembled microstructures of biocompatible and biodegradable tetraglycerol lauryl ether (C12G4) nonionic surfactant in an aqueous solvent system. Temperature-composition analyses of equilibrium phases identified by using small-angle x-ray scattering (SAXS) provide strong evidence of various spontaneously self-assembled mesostructures, such as normal micelles (Wm), hexagonal liquid crystal (H1), and reverse micelles (Om). In contrast to conventional poly(oxyethylene) nonionic surfactants, C12G4 did not exhibit the clouding phenomenon at higher temperatures (phase separation was not observed up to 100 °C), demonstrating the greater thermal stability of the self-assembled mesophases. Generalized indirect Fourier transformation (GIFT) evaluation of the SAXS data confirmed the formation of core-shell-type spherical micelles with a maximum dimension ca. 8.7 nm. The shape and size of the C12G4 micelles remained apparently unchanged over a wide range of concentrations (up to 20%), but intermicellar interactions increased and could be described by the Percus-Yevick (PY) theory (after Carnahan and Starling), which provides a very accurate analytical expression for the osmotic pressure of a monodisperse hard sphere.

  18. 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....

  19. Biomimetic peptide nanosensors.

    Science.gov (United States)

    Cui, Yue; Kim, Sang N; Naik, Rajesh R; McAlpine, Michael C

    2012-05-15

    The development of a miniaturized sensing platform tailored for sensitive and selective detection of a variety of biochemical analytes could offer transformative fundamental and technological opportunities. Due to their high surface-to-volume ratios, nanoscale materials are extremely sensitive sensors. Likewise, peptides represent robust substrates for selective recognition due to the potential for broad chemical diversity within their relatively compact size. Here we explore the possibilities of linking peptides to nanosensors for the selective detection of biochemical targets. Such systems raise a number of interesting fundamental challenges: What are the peptide sequences, and how can rational design be used to derive selective binders? What nanomaterials should be used, and what are some strategies for assembling hybrid nanosensors? What role does molecular modeling play in elucidating response mechanisms? What is the resulting performance of these sensors, in terms of sensitivity, selectivity, and response time? What are some potential applications? This Account will highlight our early attempts to address these research challenges. Specifically, we use natural peptide sequences or sequences identified from phage display as capture elements. The sensors are based on a variety of nanomaterials including nanowires, graphene, and carbon nanotubes. We couple peptides to the nanomaterial surfaces via traditional surface functionalization methods or self-assembly. Molecular modeling provides detailed insights into the hybrid nanostructure, as well as the sensor detection mechanisms. The peptide nanosensors can distinguish chemically camouflaged mixtures of vapors and detect chemical warfare agents with sensitivities as low as parts-per-billion levels. Finally, we anticipate future uses of this technology in biomedicine: for example, devices based on these sensors could detect disease from the molecular components in human breath. Overall, these results provide a

  20. Cellular and physiological effects of C-peptide.

    Science.gov (United States)

    Hills, Claire E; Brunskill, Nigel J

    2009-04-01

    In recent years, accumulating evidence indicates a biological function for proinsulin C-peptide. These results challenge the traditional view that C-peptide is essentially inert and only useful as a surrogate marker of insulin release. Accordingly, it is now clear that C-peptide binds with high affinity to cell membranes, probably to a pertussis-toxin-sensitive G-protein-coupled receptor. Subsequently, multiple signalling pathways are potently and dose-dependently activated in multiple cell types by C-peptide with the resulting activation of gene transcription and altered cell phenotype. In diabetic animals and Type 1 diabetic patients, short-term studies indicate that C-peptide also enhances glucose disposal and metabolic control. Furthermore, results derived from animal models and clinical studies in Type 1 diabetic patients suggest a salutary effect of C-peptide in the prevention and amelioration of diabetic nephropathy and neuropathy. Therefore a picture of Type 1 diabetes as a dual-hormone-deficiency disease is developing, suggesting that the replacement of C-peptide alongside insulin should be considered in its management. PMID:19243312