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Sample records for amphiphilic short peptides

  1. Peptide Amphiphiles in Corneal Tissue Engineering

    Directory of Open Access Journals (Sweden)

    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.

  2. 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...

  3. 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

  4. Effect of peptide secondary structure on peptide amphiphile supramolecular structure and interactions

    OpenAIRE

    Missirlis, Dimitris; Chworos, Arkadiusz; Fu, Caroline J; Khant, Htet A.; Krogstad, Daniel V.; Tirrell, Matthew

    2011-01-01

    Bottom-up fabrication of self-assembled nanomaterials requires control over forces and interactions between building blocks. We here report on the formation and architecture of supramolecular structures constructed from two different peptide amphiphiles. Inclusion of four alanines between a 16-mer peptide and a 16-carbon long aliphatic tail resulted in a secondary structure shift of the peptide headgroups from alpha helices to beta sheets. A concomitant shift in self-assembled morphology from...

  5. 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.

  6. Thermoplasmonic effect of silver nanoparticles modulates peptide amphiphile fiber into nanowreath-like assembly

    Science.gov (United States)

    Mishra, Narendra Kumar; Kumar, Vikas; Joshi, Khashti Ballabh

    2015-11-01

    This study demonstrates the beneficial role of di-tryptophan containing short peptide amphiphiles (sPA), for the synthesis and stabilization of AgNPs in the presence of sunlight followed by garlanding of AgNPs along the fibrous network of sPA. Such hybrid structures were precisely and selectively moulded into a nanowreath-type morphology due to the thermoplasmonic effect of AgNPs, and can be used for several bio-nanotechnological applications.This study demonstrates the beneficial role of di-tryptophan containing short peptide amphiphiles (sPA), for the synthesis and stabilization of AgNPs in the presence of sunlight followed by garlanding of AgNPs along the fibrous network of sPA. Such hybrid structures were precisely and selectively moulded into a nanowreath-type morphology due to the thermoplasmonic effect of AgNPs, and can be used for several bio-nanotechnological applications. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr06577a

  7. 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 ...

  8. Self-assembly of a peptide amphiphile: transition from nanotape fibrils to micelles

    OpenAIRE

    Miravet Celades, Juan Felipe; Escuder Gil, Beatriu; Segarra Maset, María Dolores; Tena Solsona, Marta; Hamley, Ian W.; Dehsorkhi, Ashkan; Castelletto, Valeria

    2013-01-01

    A thermal transition is observed in the peptide amphiphile C16-KTTKS (TFA salt) from nanotapes at 20 °C to micelles at higher temperature (the transition temperature depending on concentration). The formation of extended nanotapes by the acetate salt of this peptide amphiphile, which incorporates a pentapeptide from type I procollagen, has been studied previously [V. Castelletto et al., Chem. Commun., 2010, 46, 9185]. Here, proton NMR and SAXS provide evidence for the TFA salt spherical micel...

  9. Self-assembly of a peptide amphiphile: transition from nanotape fibrils to micelles

    OpenAIRE

    Miravet, Juan F.; Escuder, Beatriu; Segarra-Maset, Maria Dolores; Tena-Solsona, Marta; Hamley, Ian W.; Dehsorkhi, Ashkan; Castelletto, Valeria

    2013-01-01

    A thermal transition is observed in the peptide amphiphile C16-KTTKS (TFA salt) from nanotapes at 20 degrees C to micelles at higher temperature (the transition temperature depending on concentration). The formation of extended nanotapes by the acetate salt of this peptide amphiphile, which incorporates a pentapeptide from type I procollagen, has been studied previously [V. Castelletto et al., Chem. Commun., 2010, 46, 9185]. Here, proton NMR and SAXS provide evidence for the TFA salt spherica...

  10. 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

  11. 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

  12. 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...

  13. 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.

  14. 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

  15. Neurobioactive peptide amphiphile nanofiber scaffolds for spinal cord repair

    Science.gov (United States)

    Niece, Krista Lynne

    This thesis describes a set of peptide amphiphiles (PAs) designed for spinal cord repair (SCI). These PAs self: assemble under physiological conditions into nanofibers that cause macroscopic gelation. Hydrogen bonding, hydrophobicity, and electrostatics, which control the self-assembly, are compared throughout this thesis. PA performance is explored from a materials science and a bioengineering perspective. The salt-triggered gelation of three PAs with similar charge distributions, each bearing the neurite-outgrowth-promoting laminin-1 epitope IKVAV, is studied by rheology in Chapter 2. Stiffer, more hydrophilic PAs gel more slowly, as verified by testing analogous PAs bearing the fibronectin epitope RGD. Circular dichroism (CD) and turbidity suggest a nucleated self-assembly mechanism that depends on preexisting aggregates. Slowing gelation assists PA injection into the mouse spinal cord. Mouse neural progenitor cell (mNPC) studies with the IKVAV-PAs show cell survival, neurite outgrowth and selective neuronal differentiation, which may improve SCI repair by preventing glial scarring. Two PAs containing another laminin-1 epitope, YIGSR, are described in Chapter 3. In a negatively charged YIGSR-bearing PA (YIGSR-PA), mNPCs behave as in the IKVAV-bearing PAs, but grow longer neurites possibly due to epitope signaling. A positively charged YIGSR-bearing PA (Pos-YIGSR-PA) does not support mNPC survival. P19 cell line studies and zeta-potential measurements show that cell death is due to the PA substrate's surface charge and is specific to mNPCs. Mixed IKVAV-PA/YIGSR-PA scaffolds show averaging of cell behavior, while IKVAV-PA/Pos-YIGSR-PA mixtures fail to rescue cell viability. These dual-epitope scaffolds are studied in Chapter 4 by nuclear magnetic resonance (NMR) and CD. The like-charged mixture is composed of single-component fibers forming an interpenetrating network (IPN). The oppositely charged mixture is composed of mixed fibers, as predicted from simulation

  16. 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

  17. 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

  18. 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.

  19. Hybrid biomimetic scaffold composed of electrospun polycaprolactone nanofibers and self-assembled peptide amphiphile nanofibers

    OpenAIRE

    Tambralli, Ajay; Blakeney, Bryan; Anderson, Joel; Kushwaha, Meenakshi; Andukuri, Adinarayana; Dean, Derrick; Jun, Ho-Wook

    2009-01-01

    Nanofibrous electrospun poly (ε-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...

  20. 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...

  1. Mineralization of Peptide Amphiphiles Nanofibers and its Effect on Differentiation of Human Mesenchymal Stem Cells

    OpenAIRE

    Sargeant, Timothy D; Aparicio, Conrado; Goldberger, Josh; Cui, Honggang; Stupp, Samuel I.

    2012-01-01

    One of the important targets in regenerative medicine is to design resorbable materials that can promote formation of new bone in large skeletal defects. One approach to this challenge is to use a bioactive and biodegradable organic matrix that can promote cellular adhesion and direct differentiation. We studied here matrices composed of peptide amphiphiles (PAs) that self-assemble into nanofibers and create self-supporting gels in cell culture conditions. The bioactivity of PAs was designed ...

  2. Membrane interactions of synthetic peptides with antimicrobial potential: effect of electrostatic interactions and amphiphilicity.

    Science.gov (United States)

    Fillion, Matthieu; Valois-Paillard, Geneviève; Lorin, Aurélien; Noël, Mathieu; Voyer, Normand; Auger, Michèle

    2015-03-01

    Cationic antimicrobial peptides are considered promising candidates to complement currently used antibiotics, which are less effective against increasingly resistant pathogens. To determine the mechanism of action of these peptides, a better understanding of each molecular determinant involved in their membrane interactions is of great importance. In this study, we have focused on the role of electrostatic interactions and amphiphilicity on the membrane interactions since the large majority of natural antimicrobial peptides are cationic. Therefore, cationic and anionic peptides have been prepared based on a model 14-mer peptide. The latter is a synthetic peptide composed of ten leucines and four phenylalanines, which are modified by the addition of the crown ether. Infrared spectroscopy results indicate that the position of substitution is the main determinant involved in the secondary structure adopted by the peptides, and not the charge of the substituted residues. Fluorescence vesicle leakage assays indicate, however, differences between the ability of cationic and anionic peptides to induce calcein release in zwitterionic and anionic lipid vesicles, suggesting an importance of electrostatic interactions and repulsions. Finally, (31)P NMR results indicate that the vesicle morphologies is not significantly affected by the interactions with both cationic and anionic peptides but that their effect on lipid bilayers is mainly determined by their secondary structure. This study therefore indicates that the membrane interactions of model 14-mer peptides are mainly governed by their secondary structure, which depends on the position of substitution, and not the charge of the residues. PMID:25422123

  3. Effect of N-terminal amphiphilic peptide region on aggregation of ovalbumin

    International Nuclear Information System (INIS)

    Aggregation of protein is widely observed in our daily life. For example, cooking is manipulation of protein state. Main cause of various human diseases such as Alzheimer’s and Parkinson’s diseases is also considered to be aggregation of protein. One of model proteins is ovalbumin (OVA), which is a major protein in egg white. An OVA aqueous solution aggregates at high temperature and forms gel like sunny-side up above the threshold concentration. This phenomenon has been researched thoroughly from the viewpoint of turbidity, rheology, spectroscopy, scattering and so on. Then we, as chemists, think the next step for this research is manipulation of the aggregation state by modifying the chemical structure. Kawachi et al. concentrated on the N-terminal amphiphilic peptide region (pN1-22) and proved that this peptide region enhances the strength of OVA gel from the viewpoint of rheology. In contrast, aggregation ability of OVA without this peptide region (pOVA) is dramatically reduced. We assume that the reason for this phenomenon originates from the amphiphilic nature of the peptide. The aim of this research is to clarify the role of pN1-22 and the relationship between the microscopic chemical structure and the macroscopic physical properties. To clarify the mesoscopic structure, we conducted a SANS measurement at GP-SANS, High Flux Isotope Reactor at ORNL. Samples are solutions or gels of OVA, pOVA, peptide and their mixture with various concentrations before and after heating. pH of samples was set to 7, which is common condition for the application of OVA and their derivatives. We observed a strong upturn at low-q region in SANS curves for pOVA solutions/gels after heating. This behavior is similar to a phase separation of well-known poly(N-isopropylacrylamide) (PNIPA) solutions. From this result, we can see that the lack of amphiphilic peptide region makes the OVA solute unstable and promotes aggregation. In contrast to this, addition of amphiphilic peptide

  4. 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

  5. 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.

  6. 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 ...

  7. Modulating self-assembly behavior of a salt-free peptide amphiphile (PA) and zwitterionic surfactant mixed system.

    Science.gov (United States)

    Zhang, Han; Sun, Jichao; Xin, Xia; Xu, Wenlong; Shen, Jinglin; Song, Zhaohua; Yuan, Shiling

    2016-04-01

    A salt-free surfactant system formed by a peptide amphiphile with short headgroup (PA,C16-GK-3) and a zwitterionic surfactant (dodecyldimethylamine oxide, C12DMAO) in water has been systematically investigated. The microstructures and properties of C16-GK-3/C12DMAO mixed system were characterized using a combination of microscopic, scattering and spectroscopic techniques, including transmission electron microscopy (TEM), field emission-scanning electron microscopy (FE-SEM), atomic force microscopy (AFM), Fourier transform infrared (FT-IR), circular dichroism (CD) and rheological measurements. Rich phase transitions have been observed by adjusting the concentration of C16-GK-3. Investigation of the hydrogels of C16-GK-3/C12DMAO with TEM, SEM and AFM showed that all of these hydrogels form nanobelts. The nanobelt formation is performed in a hierarchical manner: β-sheet peptides and C12DMAO first interact each other to form small aggregates, which then arrange themselves to form one dimensional (1D) left-handed ribbons. The ribbons further aggregated into flat and rigid nanobelts. We proposed a mechanism to interpret the self-assembly process according to the specific peptide structure as well as multiple equilibria between the hydrogen bonding interactions between the headgroups of C16-GK-3, between C12DMAO molecules and the headgroups of C16-GK-3, chirality of the amino acid residues and hydrophobic interactions of the alkyl chains. PMID:26773608

  8. 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

  9. 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.

  10. 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

  11. 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

  12. 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.

  13. 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.

  14. Amphiphilic glycopolymer nanoparticles as vehicles for nasal delivery of peptides and proteins.

    Science.gov (United States)

    Zheng, Chao; Guo, Qianqian; Wu, Zhongming; Sun, Lei; Zhang, Zhengpu; Li, Chaoxing; Zhang, Xinge

    2013-07-16

    Nasal drug delivery system has been a very promising route for delivery of proteins and peptides for the reason that it can avoid degradation in gastrointestinal tract and metabolism by liver enzymes. However, the bioavailability of proteins and peptides is still low due to the rapid clearance of mucociliary. Here, to prolong the residence time of drugs and improve their absorption, we prepared amphiphilic glycopolymer poly(2-lactobionamidoethyl methacrylate-random-3-acrylamidophenylboronic acid) (p(LAMA-r-AAPBA), and the glycopolymer could assemble into the nanoparticles with narrow size distribution. Insulin, as a model drug, was efficiently encapsulated within the nanoparticles, and loading capacity was up to 12%. In vitro study revealed that the insulin release could be controlled by modifying the composition of glycopolymers. Cell viability showed that p(LAMA-r-AAPBA) nanoparticles had good cytocompatibility. Moreover, the mechanism of nanoparticle internalization into Calu-3 cells was a combination mechanism of clathrin-mediated endocytosis and lipid raft/caveolae-mediated endocytosis. Importantly, there was a significant decrease in the blood glucose levels after the nasal administration of p(LAMA-r-AAPBA) nanoparticles to diabetic rats. Therefore, p(LAMA-r-AAPBA) glycopolymers have a potential application as a nasal delivery systems for proteins and peptides. PMID:23648782

  15. 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...

  16. 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

  17. 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

  18. 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

  19. 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...

  20. 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

  1. 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

  2. Exploring architectures at the nanoscale: the interplay between hydrophobic twin lipid chains and head groups of designer peptide amphiphiles in the self-assembly process and application.

    Science.gov (United States)

    Dasgupta, Antara

    2016-05-11

    The self-assembly of peptide amphiphiles (PAs) is found to be governed by the hydrophobic interactions induced by the hydrophobic groups/number of alkyl chains and the hydrophilic head groups. In this study, an assessment of the nanostructures formed by the self-assembly of simple twin chained PAs was carried out and compared to their single chain/short analogues. The spectroscopic and microscopic analysis revealed the fact that the twin chained amphiphiles had a high inclination to form β-sheet nanofibers and further towards hydrogelation. The mixture of twin chained PAs also exhibited cooperative self-assembly with improved aggregation behavior, although not much augmentation in β-type structuring was found. In contrast, the single chain/short analogue containing PAs showed very less of β-sheet type structures to a lesser extent and no hydrogelating behavior but resulted in mostly random conformations. The increase in the number or alteration of polar head groups in double chained PAs induced higher extent of β-type conformation and better gelling capability due to the combined hydrophobic effect of the twin chains. The overall results delineated the dominance of hydrophobic interactions. Finally, calcium phosphate bio-mineralization was done in the hydrogels of twin chained PAs with the aim of developing future biomaterials. PMID:27079384

  3. Antimalarial Activity of Ultra-Short Peptides

    Directory of Open Access Journals (Sweden)

    María Yolanda Rios

    2009-12-01

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

  4. 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.

  5. RGD-bearing peptide-amphiphile-hydroxyapatite nanocomposite bone scaffold: an in vitro study

    International Nuclear Information System (INIS)

    In this study, a fibrous nanocomposite scaffold was developed by combining hydroxyapatite (HA) fibers produced by electrospinning method and arginine–glycine–aspartic acid (RGD)-bearing peptide-amphiphile (PA) gel (PA-RGD) produced by self-assembly and gelation induced by calcium ions. Scanning electron microscope, transmission electron microscope and atomic force microscopy imaging confirmed the successful production of inorganic and organic components of this nanocomposite material. Within the HA, the presence of a CaCO3 phase, improving biodegradation, was shown by x-ray diffraction analysis. The in vitro effectiveness of the PA-RGD/HA scaffold was determined on MC3T3-E1 preosteoblast cultures in comparison with HA matrix and PA-RGD gel. The highest cellular proliferation was obtained on PA-RGD gel, however, alkaline phosphatase activity results denoted that osteogenic differentiation of the cells is more favorable on HA containing matrices with respect to PA-RGD itself. Microscopic observations revealed that all three matrices support cell attachment and proliferation. Moreover, cells form bridges between the HA and PA-RGD components of the nanocomposite scaffold, indicating the integrity of the biphasic components. According to the real time-polymerase chain reaction (RT-PCR) analyses, MC3T3-E1 cells expressed significantly higher osteocalcin on all matrices. Bone sialoprotein (BSP) expression level is ten-fold higher on PA-RGD/HA nanocomposite scaffolds than that of HA and PA-RGD scaffolds and the elevated expression of BSP on PA-RGD/HA nanocomposite scaffolds suggested higher mineralized matrix on this novel scaffold. Based on the results obtained in this study, the combination of HA nanofibers and PA-RGD gel takes advantage of good structural integrity during the cell culture, besides the osteoinductive and osteoconductive properties of the nanofibrous scaffold. (paper)

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

    International Nuclear Information System (INIS)

    Nanofibrous electrospun poly (ε-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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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)

  15. 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

  16. 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...

  17. 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

  18. 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

  19. 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.

  20. 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.

  1. Molecular mechanical properties of short-sequence peptide enzyme mimics.

    Science.gov (United States)

    Takahashi, Tsukasa; Vo Ngo, Bao C; Xiao, Leyang; Arya, Gaurav; Heller, Michael J

    2016-03-01

    While considerable attempts have been made to recreate the high turnover rates of enzymes using synthetic enzyme mimics, most have failed and only a few have produced minimal reaction rates that can barely be considered catalytic. One particular approach we have focused on is the use of short-sequence peptides that contain key catalytic groups in close proximity. In this study, we designed six different peptides and tested their ability to mimic the catalytic mechanism of the cysteine proteases. Acetylation and deacylation by Ellman's Reagent trapping experiments showed the importance of having phenylalanine groups surrounding the catalytic sites in order to provide greater proximity between the cysteine, histidine, and aspartate amino acid R-groups. We have also carried out all-atom molecular dynamics simulations to determine the distance between these catalytic groups and the overall mechanical flexibility of the peptides. We found strong correlations between the magnitude of fluctuations in the Cys-His distance, which determines the flexibility and interactions between the cysteine thiol and histidine imidazole groups, and the deacylation rate. We found that, in general, shorter Cys-His distance fluctuations led to a higher deacylation rate constant, implying that greater confinement of the two residues will allow a higher frequency of the acetyl exchange between the cysteine thiol and histidine imidazole R-groups. This may be the key to future design of peptide structures with molecular mechanical properties that lead to viable enzyme mimics. PMID:25921736

  2. 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

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

    International Nuclear Information System (INIS)

    The effect of short and medium chain length alcohols ethanol, propanol, and butanol on the thermodynamic properties of aqueous solutions of the ionic amphiphilic antidepressants imipramine and clomipramine hydrochlorides has been investigated at T = 293 K. Critical concentrations of the drugs were obtained from ultrasound velocity measurements. Experimental results have shown a strong dependence of the ultrasound velocity with the alcohol concentration and chain length. Differences in the aggregate properties of both amphiphiles arise from the presence of the extra Cl- substituent on the ring system of clomipramine. Density and ultrasound measurements have been used to obtain the apparent molar volumes, Vφ, and isentropic apparent molar compressibilities, Kφ(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, ΔG0, phase was calculated from the partition coefficient. The results have highlighted the structural differences between both amphiphiles

  4. 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.

  5. Discriminating self from nonself with short peptides from large proteomes

    DEFF Research Database (Denmark)

    Burrouhgs, N.J.; Boer, R.J.; Kesmir, Can

    2004-01-01

    information. Our results show that this is not the case because the HLA molecules are fairly specific. Removing the two anchor residues from each presented peptide, we find that the self:nonself overlap of these exposed 7-mers resembles that of 9-mers. Summarizing, the 9-mers used in MHC class I presentation...... tend to carry sufficient information to detect nonself peptides amongst self peptides....

  6. 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.

  7. 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.

  8. 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

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

    International Nuclear Information System (INIS)

    Research highlights: → Short antimicrobial peptides with nine and eleven residues were developed. → These peptides show strong bactericidal activity against clinically important bacterial and fungal pathogens. → These peptides exhibit high stability in the presence of salts, and low cytotoxicity. → 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 μg ml-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 μg ml-1 against four of the tested pathogens; these MICs are two to eight times lower than those reported for Pac-525 (6.2-50 μg ml-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.

  10. 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.

  11. 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...

  12. 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

  13. 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.

  14. 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

  15. 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

  16. A fluorimetric study on the interaction between a Trp-containing beta-strand peptide and amphiphilic polymer-coated gold nanoparticles.

    Science.gov (United States)

    Yuan, Ming; Zhong, Ruibo; Yun, Xiaoling; Hou, Jiahua; Du, Qiqige; Zhao, Guofen; Zhang, Feng

    2016-02-01

    Owing to the inevitability of nanoparticles encountering proteins/peptides in current bio-nano-medicine development, it is important to know how they interact with each other in vitro before developing in vivo applications. To this end, a model de novo β-sheet-forming peptide and typical biocompatible nanoparticles were selected to study thermodynamic aspects of their interactions via a fluorescence quenching method. The results showed that Pep11 and AuNPs spontaneously formed conjugates, mainly driven by a coulombic interaction with a binding affinity of ~ 0.1 µM(-1); the physical adsorption process was cooperative. These results deepen our quantitative understanding of nanoparticle-peptide interactions. The results may also be helpful in further nanoparticle-peptide hybrid nanofabrication and also useful for the application of nanoparticles in the treatment of amyloid diseases. PMID:25920412

  17. Thermodynamic characterization of an artificially designed amphiphilic alpha-helical peptide containing periodic prolines: observations of high thermal stability and cold denaturation.

    OpenAIRE

    Kitakuni, E.; Kuroda, Y; Oobatake, M.; Tanaka, T; Nakamura, H

    1994-01-01

    To investigate the structural stability of proteins, we analyzed the thermodynamics of an artificially designed 30-residue peptide. The designed peptide, NH2-EELLPLAEALAPLLEALLPLAEALAPLLKK-COOH (PERI COIL-1), with prolines at i + 7 positions, forms a pentameric alpha-helical structure in aqueous solution. The thermal denaturation curves of the CD at 222 nm (pH 7.5) show an unusual cold denaturation occurring well above 0 degrees C and no thermal denaturation is observable under 90 degrees C. ...

  18. 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

  19. 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

  20. 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

  1. Fusion of a Short HA2-Derived Peptide Sequence to Cell-Penetrating Peptides Improves Cytosolic Uptake, but Enhances Cytotoxic Activity

    Directory of Open Access Journals (Sweden)

    Igor Kitanovic

    2009-09-01

    Full Text Available Cell-penetrating peptides (CPP have become a widely used tool for efficient cargo delivery into cells. However, one limiting fact is their uptake by endocytosis causing the enclosure of the CPP-cargo construct within endosomes. One often used method to enhance the outflow into the cytosol is the fusion of endosome-disruptive peptide or protein sequences to CPP. But, until now, no studies exist investigating the effects of the fusion peptide to the cellular distribution, structural arrangements and cytotoxic behaviour of the CPP. In this study, we attached a short modified sequence of hemagglutinin subunit HA2 to different CPP and analysed the biologic activity of the new designed peptides. Interestingly, we observed an increased cytosolic distribution but also highly toxic activities in the micromolar range against several cell lines. Structural analysis revealed that attachment of the fusion peptide had profound implications on the whole conformation of the peptide, which might be responsible for membrane interaction and endosome disruption.

  2. Inhibition of the myostatin/Smad signaling pathway by short decorin-derived peptides.

    Science.gov (United States)

    El Shafey, Nelly; Guesnon, Mickaël; Simon, Françoise; Deprez, Eric; Cosette, Jérémie; Stockholm, Daniel; Scherman, Daniel; Bigey, Pascal; Kichler, Antoine

    2016-02-15

    Myostatin, also known as growth differentiation factor 8, is a member of the transforming growth factor-beta superfamily that has been shown to play a key role in the regulation of the skeletal muscle mass. Indeed, while myostatin deletion or loss of function induces muscle hypertrophy, its overexpression or systemic administration causes muscle atrophy. Since myostatin blockade is effective in increasing skeletal muscle mass, myostatin inhibitors have been actively sought after. Decorin, a member of the small leucine-rich proteoglycan family is a metalloprotein that was previously shown to bind and inactivate myostatin in a zinc-dependent manner. Furthermore, the myostatin-binding site has been shown to be located in the decorin N-terminal domain. In the present study, we investigated the anti-myostatin activity of short and soluble fragments of decorin. Our results indicate that the murine decorin peptides DCN48-71 and 42-65 are sufficient for inactivating myostatin in vitro. Moreover, we show that the interaction of mDCN48-71 to myostatin is strictly zinc-dependent. Binding of myostatin to activin type II receptor results in the phosphorylation of Smad2/3. Addition of the decorin peptide 48-71 decreased in a dose-dependent manner the myostatin-induced phosphorylation of Smad2 demonstrating thereby that the peptide inhibits the activation of the Smad signaling pathway. Finally, we found that mDCN48-71 displays a specificity towards myostatin, since it does not inhibit other members of the transforming growth factor-beta family. PMID:26844629

  3. 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.

  4. Second harmonic generation from tryptophan-rich short peptides: W(n)K(m) and gramicidin A.

    Science.gov (United States)

    Duboisset, J; Matar, G; Besson, F; Ficheux, D; Benichou, E; Russier-Antoine, I; Jonin, Ch; Brevet, P F

    2014-09-01

    We report the first hyperpolarizability of a series of tryptophan-rich short peptides with the respective sequence KWK, KWWK, KWWWK, KWWKWWK, where W and K stand for tryptophan and lysine. The measurements were performed with the technique of hyper-Rayleigh scattering in the bulk of an aqueous Tris buffer solution at a pH of 8.5 and a salt concentration of 150 mM at the non-resonant fundamental wavelength of 784 nm. The first hyperpolarizability of the different peptides follows a simple additive model scaling with the number of tryptophan residues contained in the peptide. However, it appears that the first hyperpolarizability response of a single tryptophan residue in the peptide strongly differs from that of an isolated tryptophan. Hence, it is therefore demonstrated that the local environment of the tryptophan residues within the peptide strongly influences its nonlinear optical response. A comparison with the first hyperpolarizability of the natural peptide gramicidin A measured in trifluoroethanol (TFE) further confirms the key role of the local environment on the first hyperpolarizability of tryptophan residues in peptides. PMID:25144248

  5. Short-peptide fusion inhibitors with high potency against wild-type and enfuvirtide-resistant HIV-1.

    Science.gov (United States)

    Chong, Huihui; Yao, Xue; Qiu, Zonglin; Sun, Jianping; Zhang, Meng; Waltersperger, Sandro; Wang, Meitian; Liu, Shan-Lu; Cui, Sheng; He, Yuxian

    2013-03-01

    Peptides derived from the C-terminal heptad repeat (C peptides) of HIV-1 gp41 are potent inhibitors against virus entry. However, development of a short C peptide possessing high anti-HIV potency is considered a daunting challenge. We recently discovered that the residues Met626 and Thr627 preceding the pocket-binding domain of the C peptide adopt a unique M-T hook structure that is crucial for the design of HIV-1 fusion inhibitors. In this study, we first presented a proof-of-concept prototype that the M-T hook residues can dramatically improve the antiviral activity and thermostability of a short C peptide. We then generated a 24-mer peptide termed MT-SC22EK by incorporating the M-T hook structure to the N terminus of the poorly active short C peptide SC22EK. Amazingly, MT-SC22EK inhibited HIV-1-mediated cell fusion and infection at a level comparable to C34, T1249, SC29EK, and sifuvirtide, and it was highly active against diverse HIV-1 subtypes and variants, including those T20 (enfuvirtide) and SC29EK-resistant viruses. The high-resolution crystal structure of MT-SC22EK reveals the N-terminal M-T hook conformation folded by incorporated Met626 and Thr627 and identifies the C-terminal boundary critical for the anti-HIV activity. Collectively, our studies provide new insights into the mechanisms of HIV-1 fusion and its inhibition. PMID:23233535

  6. 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 ...... that included a significant increase in total body bone mass. This article describes the effect of GLP-2 on spinal and hip bone mineral density (BMD) and biochemical markers of bone turnover in these patients.......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...

  7. 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...

  8. A comparison between the recombinant expression and chemical synthesis of a short cysteine-rich insecticidal spider peptide

    OpenAIRE

    Clement, Herlinda; Flores, Vianey; Diego-Garcia, Elia; Corrales-Garcia, Ligia; Villegas, Elba; Corzo, Gerardo

    2015-01-01

    Background The choice between heterologous expression versus chemical synthesis for synthesizing short cysteine-rich insecticidal peptides from arthropods may impact the obtainment of yields and well-folded bioactive molecules for scientific research. Therefore, two recombinant expression systems were compared to that of chemical synthesis for producing Ba1, a cysteine-rich spider neurotoxin. Methods The transcription of the insecticidal neurotoxin Ba1 was obtained from a cDNA library of veno...

  9. 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.

  10. 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

  11. Interaction between dietary bioactive peptides of short length and bile salts in submicellar or micellar state.

    Science.gov (United States)

    Guerin, Justine; Kriznik, Alexandre; Ramalanjaona, Nick; Le Roux, Yves; Girardet, Jean-Michel

    2016-10-15

    Bile salts act as steroidal detergents in the gut, and could also interact with peptides and improve their bioavailability, although the mechanism is unclear. The occurrence of direct interaction between milk bioactive peptides, Ile-Asn-Tyr-Trp, Leu-Asp-Gln-Trp, and Leu-Gln-Lys-Trp, and different bile salts in the submicellar or micellar state was investigated by intrinsic fluorescence measurement and dynamic light scattering, above the critical micellar concentration, the latter being determined by isothermal titration calorimetry. The peptides form aggregates, spontaneously. In the presence of bile salts, some released peptide monomers were bound to the micellar surface. The lack of hydrogen bonding involving the C12OH group of the steroid skeleton, and the acidic function of some bile salts, might promote the interaction with the peptides, as could the lack of the C12OH group, rather than that of the C7OH group. At submicellar concentrations, sodium taurochenodeoxycholate and taurodeoxycholate readily interacted with the most hydrophobic peptide Ile-Asn-Tyr-Trp. PMID:27173542

  12. 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

  13. 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

  14. 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.

  15. 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.

  16. Self-assembly and adsorption properties of Fmoc-substituted short peptide bearing charged side chains

    Science.gov (United States)

    Nakayama, Toru; Sakuraba, Taro; Yamamoto, Yohei

    2015-12-01

    Charge-separated peptide β-sheet with a positive charge on one side and a negative charge on the other side adsorbed on a mica surface with well-ordered geometry along the crystallographic direction of the mica surface. In MeOH and MeOH/H2O mixed solvent, the peptides do not form β-sheet structure. During the evaporation process of the solvent on a mica substrate, the peptides self-assembled to form β-sheet and adsorb on the surface via electrostatic interaction between negative charge of the mica surface and positive charge of the lysine side chain on one side of the β-sheet.

  17. 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.

  18. 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

  19. 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...

  20. Short- and long-term influences of calcitonin gene-related peptide on the synthesis of acetylcholinesterase in mammalian myotubes

    OpenAIRE

    da Costa, Valter Luiz; Lapa, Antonio José; Godinho, Rosely O.

    2001-01-01

    The present study analyses the short- (15 min – 2 h) and long-term (24 – 48 h) influences of calcitonin gene-related peptide (CGRP) on acetylcholinesterase (AChE) expression in the rat cultured skeletal muscle and the signal transduction events underlying CGRP actions.To assess the effect of CGRP on AChE synthesis, myotubes were pre-exposed to the irreversible AChE inhibitor diisopropyl fluorophosphate (DFP) and treated with CGRP or forskolin, an adenylyl cyclase (AC) activator. Treatment of ...

  1. Study of low-frequency dynamics of short peptides by Brillouin light scattering and Monte-Carlo global energy minimization

    International Nuclear Information System (INIS)

    Brillouin light scattering studies of the behavior of hypersound velocity in solutions of short peptides Asp-Ser, Glu-Asp-Arg, Ala-Glu-Asp-Leu with widely varying concentrations at temperatures ranging from 295 to 360K are presented. As shown by analysis of experimental data and molecular simulation, the dipeptide Asp-Ser is characterized by formation of dimers which decompose at high temperatures. High-concentration solutions of tri- and tetrapeptides form aggregates at high temperatures which are preserved on cooling

  2. 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

  3. Design of a predicted MHC restricted short peptide immunodiagnostic and vaccine candidate for Fowl adenovirus C in chicken infection

    OpenAIRE

    Valdivia-Olarte, Hugo; Requena, David; Ramirez, Manuel; Saravia, Luis E; Izquierdo, Ray; Falconi-Agapito, Francesca; Zavaleta, Milagros; Best, Iván; Fernández-Díaz, Manolo; Zimic, Mirko

    2015-01-01

    Fowl adenoviruses (FAdVs) are the ethiologic agents of multiple pathologies in chicken. There are five different species of FAdVs grouped as FAdV-A, FAdV-B, FAdV-C, FAdV-D, and FAdV-E. It is of interest to develop immunodiagnostics and vaccine candidate for Peruvian FAdV-C in chicken infection using MHC restricted short peptide candidates. We sequenced the complete genome of one FAdV strain isolated from a chicken of a local farm. A total of 44 protein coding genes were identified in each gen...

  4. 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

  5. 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

  6. Self-Assembly of Peptides at the Air/Water Interface

    Science.gov (United States)

    Sayar, Mehmet

    2013-03-01

    Peptides are commonly used as building blocks for design and development of novel materials with a variety of application areas ranging from drug design to biotechnology. The precise control of molecular architecture and specific nature of the nonbonded interactions among peptides enable aggregates with well defined structural and functional properties. The interaction of peptides with interfaces leads to dramatic changes in their conformational and aggregation behavior. In this talk, I will discuss our research on the interplay of intermolecular forces and influence of interfaces. In the first part the amphiphilic nature of short peptide oligomers and their behavior at the air/water interface will be discussed. The surface driving force and its decomposition will be analyzed. In the second part aggregation of peptides in bulk water and at an interface will be discussed. Different design features which can be tuned to control aggregation behavior will be analyzed.

  7. 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 test...

  8. Structural development of stapled short helical peptides as vitamin D receptor (VDR)-coactivator interaction inhibitors.

    Science.gov (United States)

    Misawa, Takashi; Demizu, Yosuke; Kawamura, Megumi; Yamagata, Nanako; Kurihara, Masaaki

    2015-03-01

    We developed several stabilized helical heptapeptides (DPI-01-10) composed of l-leucine residues, an α,α-disubstituted α-amino acid (α-aminoisobutyric acid [Aib] or hydroxymethylserine [Hms]), and a stapled side chain as inhibitors of vitamin D receptor (VDR)-coactivator interactions. The inhibitory activity of these peptides against VDR-coactivator interactions was evaluated using a receptor cofactor assay system, and DPI-08 demonstrated strong activity (IC50: 3.2μM). PMID:25637122

  9. Acute effects of the glucagon-like peptide 2 analogue, teduglutide, on intestinal adaptation in short bowel syndrome.

    Science.gov (United States)

    Thymann, Thomas; Stoll, Barbara; Mecklenburg, Lars; Burrin, Douglas G; Vegge, Andreas; Qvist, Niels; Eriksen, Thomas; Jeppesen, Palle B; Sangild, Per T

    2014-06-01

    Neonatal short bowel syndrome following massive gut resection is associated with malabsorption of nutrients. The intestinotrophic factor glucagon-like peptide 2 (GLP-2) improves gut function in adult patients with short bowel syndrome, but its effect in pediatric patients remains unknown. Our objective was to test the efficacy of the long-acting synthetic human GLP-2 analogue, teduglutide (ALX-0600), in a neonatal piglet jejunostomy model. Two-day-old pigs were subjected to resection of 50% of the small intestine (distal part), and the remnant intestine was exteriorized on the abdominal wall as a jejunostomy. All pigs were given total parenteral nutrition for 7 days and a single daily injection of the following doses of teduglutide: 0.01 (n = 6), 0.02 (n = 6), 0.1 (n = 5), or 0.2 mg · kg · day (n = 6), and compared with placebo (n = 9). Body weight increment was similar for all 4 teduglutide groups but higher than placebo (P < 0.05). There was a dose-dependent increase in weight per length of the remnant intestine (P < 0.01) and fractional protein synthesis rate in the intestine was increased in the 0.2 mg · kg · day group versus placebo (P < 0.001); however, functional and structural endpoints including activity of digestive enzymes, absorption of enteral nutrients, and immunohistochemistry (Ki67, villin, FABP2, ChgA, and GLP-2R) were not affected by the treatment. Teduglutide induces trophicity on the remnant intestine but has limited acute effects on functional endpoints. Significant effects of teduglutide on gut function may require a longer adaptation period and/or a more frequent administration of the peptide. In perspective, GLP-2 or its analogues may be relevant to improve intestinal adaptation in pediatric patients with short bowel syndrome. PMID:24399211

  10. 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.

  11. 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.

  12. 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

  13. Peptidomic discovery of short open reading frame-encoded peptides in human cells

    OpenAIRE

    Slavoff, Sarah A.; Mitchell, Andrew J.; Schwaid, Adam G.; Cabili, Moran N; Ma, Jiao; Levin, Joshua Z.; Karger, Amir; Budnik, Bogdan A.; Rinn, John L; Saghatelian, Alan

    2012-01-01

    The amount of the transcriptome that is translated into polypeptides is of fundamental importance. We developed a peptidomic strategy to detect short ORF (sORF)-encoded polypeptides (SEPs) in human cells. We identified 90 SEPs, 86 of which are novel, the largest number of human SEPs ever reported. SEP abundances range from 10-1000 molecules per cell, identical to known proteins. SEPs arise from sORFs in non-coding RNAs as well as multi-cistronic mRNAs, and many SEPs initiate with non-AUG star...

  14. 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 ob...

  15. Teduglutide (ALX-0600), a dipeptidyl peptidase IV resistant glucagon-like peptide 2 analogue, improves intestinal function in short bowel syndrome patients

    OpenAIRE

    Jeppesen, P B; Sanguinetti, E L; Buchman, A; Howard, L.; Scolapio, J S; Ziegler, T R; Gregory, J; Tappenden, K A; Holst, J.; Mortensen, P B

    2005-01-01

    Background and aims: Glucagon-like peptide 2 (GLP-2) may improve intestinal absorption in short bowel syndrome (SBS) patients with an end jejunostomy. Teduglutide (ALX-0600), a dipeptidyl peptidase IV resistant GLP-2 analogue, prolongs the intestinotrophic properties of GLP-2 in animal models. The safety and effect of teduglutide were investigated in SBS patients with and without a colon in continuity.

  16. Amphiphiles for protein solubilization and stabilization

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-11-04

    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.

  17. 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.

  18. 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

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

    Science.gov (United States)

    Jeppesen, Palle Bekker

    2012-05-01

    Short bowel syndrome results from surgical resection, congenital defect or disease-associated loss of absorption. Parenteral support (PS) is lifesaving in patients with short bowel syndrome and intestinal failure who are unable to compensate for their malabsorption by metabolic or pharmacologic adaptation. Together, the symptoms of short bowel syndrome and the inconvenience and complications in relation to PS (e.g. catheter-related blood steam infections, central thrombosis and intestinal failure associated liver disease) may impair the quality of life of patients. The aim of treatment is to maximize intestinal absorption, minimize the inconvenience of diarrhea, and avoid, reduce or eliminate the need for PS to achieve the best possible quality of life for the patient. Conventional treatments include dietary manipulations, oral rehydration solutions, and antidiarrheal and antisecretory treatments. However, the evidence base for these interventions is limited and treatments that improve the structural and functional integrity of the remaining intestine are needed. Teduglutide, an analog of glucagon-like peptide 2, improves intestinal rehabilitation by promoting mucosal growth and possibly by restoring gastric emptying and secretion, thereby reducing intestinal losses and promoting intestinal absorption. In a 3-week, phase II balance study, teduglutide reduced diarrhea by around 700 g/day and fecal energy losses by around 0.8 MJ/day. In two randomized, placebo-controlled, 24-week, phase III studies, similar findings were obtained when evaluating the fluid composite effect, which is the sum of the beneficial effects of teduglutide - reduction in the need for PS, increase in urine production and reduction in oral fluid intake. The fluid composite effect reflects the increase in intestinal 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

  20. Teduglutide, a glucagon-like peptide-2 analog for the treatment of gastrointestinal diseases, including short bowel syndrome.

    Science.gov (United States)

    Yazbeck, Roger

    2010-12-01

    Glucagon-like peptide-2 (GLP-2) is a potent intestinotrophic growth factor with therapeutic potential for the prevention or treatment of an expanding number of gastrointestinal diseases, including short bowel syndrome (SBS). Teduglutide, being developed by NPS Allelix and licensee Nycomed, is a protease-resistant analog of GLP-2 for the potential treatment of gastrointestinal disease. Teduglutide has prolonged biological activity compared with native GLP-2, and preclinical studies demonstrated significant intestinotrophic activity in models of SBS, experimental colitis and chemotherapy-induced intestinal mucositis. Patients with SBS rely on parenteral nutrition (PN) following bowel resection, and in a phase III clinical trial with teduglutide, > 20% reduction in PN was observed in patients with SBS receiving teduglutide. A phase II clinical trial for teduglutide in Crohn's disease observed remission rates of 55.6% in patients. At the time of publication, phase III clinical trials for SBS were ongoing, as were preclinical studies for chemotherapy-induced mucositis and pediatric indications. Teduglutide represents a novel, efficacious drug capable of increasing intestinal growth and improving intestinal function, and may change clinical management of intestinal disease and damage. PMID:21154171

  1. 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...

  2. 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

  3. Phase behavior of an amphiphilic fluid.

    Science.gov (United States)

    Schoen, Martin; Giura, Stefano; Klapp, Sabine H L

    2014-01-01

    We invoke mean-field density functional theory (DFT) to investigate the phase behavior of an amphiphilic fluid composed of a hard-sphere core plus a superimposed anisometric Lennard-Jones perturbation. The orientation dependence of the interactions consists of a contribution analogous to the interaction potential between a pair of "spins" in the classical, three-dimensional Heisenberg fluid and another one reminiscent of the interaction between (electric or magnetic) point dipoles. At fixed orientation both contributions are short-range in nature decaying as r-6 (r being the separation between the centers of mass of a pair of amphiphiles). Based upon two mean-field-like approximations for the pair correlation function that differ in the degree of sophistication we derive expressions for the phase boundaries between various isotropic and polar phases that we solve numerically by the Newton-Raphson method. For sufficiently strong coupling between the Heisenberg "spins" both mean-field approximations generate three topologically different and generic types of phase diagrams that are observed in agreement with earlier work [see, for example, Tavares et al., Phys. Rev. E 52, 1915 (1995)]. Whereas the dipolar contribution alone is incapable of stabilizing polar phases on account of its short-range nature it is nevertheless important for details of the phase diagram such as location of the gas-isotropic liquid critical point, triple, and tricritical points. By tuning the dipolar coupling constant suitably one may, in fact, switch between topologically different phase diagrams. Employing also Monte Carlo simulations in the isothermal-isobaric ensemble the general topology of the DFT phase diagrams is confirmed. PMID:24580230

  4. 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

  5. Effect of Teduglutide, a Glucagon-like Peptide 2 Analog, on Citrulline Levels in Patients With Short Bowel Syndrome in Two Phase III Randomized Trials

    OpenAIRE

    Seidner, Douglas L; Joly, Francisca; Youssef, Nader N

    2015-01-01

    Objectives: In clinical trials, treatment with the glucagon-like peptide 2 analog teduglutide was associated with improved fluid and nutrient absorption and increased intestinal villus height and crypt depth in patients with short bowel syndrome (SBS). Plasma citrulline, an amino acid produced by enterocytes, is considered a measure of enterocyte mass. This analysis assessed changes in plasma citrulline levels in patients with SBS in 2 phase III clinical studies of teduglutide. Methods: Both ...

  6. 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 ...

  7. 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.

  8. 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

  9. 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

  10. 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

  11. 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

  12. Tandem Facial Amphiphiles for Membrane Protein Stabilization

    DEFF Research Database (Denmark)

    Chae, Pil Seok; Gotfryd, Kamil; Pacyna, Jennifer; Miercke, Larry J W; Rasmussen, Søren G F; Robbins, Rebecca A; Rana, Rohini R; Løland, Claus Juul; Kobilka, Brian; Stroud, Robert; Byrne, Bernadette; Gether, Ulrik; Gellman, Samuel H

    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....

  13. 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...

  14. pH-dependent Self-Assembling Behaviour of KA6 Surfactant Peptide

    DEFF Research Database (Denmark)

    Gurevich, Leonid; Fojan, Peter

    -assembling machinery toolbox for nanotechnology. Recently designed new classes of short (less than 10 amino acids) synthetic amphiphilic peptides represent important model systems [1]. Here various factors affecting self-assembling behavior can be singulated and studied one by one. Furthermore, their structure can be...... easily tailored on-demand. On the other hand they are fairly simple and inexpensive to produce and may find applications in purification and crystallization of membrane proteins, drug delivery and encapsulation systems or as mild surfactants in the cosmetic industry....

  15. 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

  16. 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 ...

  17. 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...

  18. 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

  19. 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

    BACKGROUND AND AIMS: Glucagon-like peptide 2 (GLP-2) has been shown to improve intestinal absorption in short bowel syndrome (SBS) patients in a short-term study. This study describes safety, compliance, and changes in quality of life in 11 SBS patients at baseline, week 13, 26, and 52 during two......-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 < .01), the overall SIP score...

  20. 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...

  1. 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...

  2. 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...

  3. Comparison Review of Short-Acting and Long-Acting Glucagon-like Peptide-1 Receptor Agonists

    OpenAIRE

    Uccellatore, AnnaChiara; Genovese, Stefano; Dicembrini, Ilaria; Mannucci, Edoardo; Ceriello, Antonio

    2015-01-01

    Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1 RAs) are useful tools for treating type 2 diabetes mellitus. In their recent position statement, the American Diabetes Association and European Association for the Study of Diabetes recommend GLP1-RAs as add-on to metformin when therapeutic goals are not achieved with monotherapy, particularly for patients who wish to avoid weight gain or hypoglycemia. GLP1-RAs differ substantially in their duration of action, frequency of administratio...

  4. 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.

  5. 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.

  6. 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

    adaptation. Together, the symptoms of short bowel syndrome and the inconvenience and complications in relation to PS (e.g. catheter-related blood steam infections, central thrombosis and intestinal failure associated liver disease) may impair the quality of life of patients. The aim of treatment is to......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...... 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....

  7. [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

  8. 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.

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

    Science.gov (United States)

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

    2009-12-01

    Teduglutide, a synthetic glucagon-like peptide-2 (GLP-2) analog with activity relating to the regeneration, maintenance, and repair of the intestinal epithelium, is currently being evaluated for the treatment of short-bowel syndrome (SBS), Crohn's disease, and other gastrointestinal disorders. On the basis of promising results from teduglutide studies in adults with SBS and from studies in neonatal and juvenile animal models, a pediatric multiple-dose phase I clinical study was designed to determine the safety, efficacy, and pharmacokinetics of teduglutide in pediatric patients with SBS who have undergone resection for necrotizing enterocolitis, malrotation, or intestinal atresia. This report details the application of clinical trial simulations coupled with a novel approach using generalized additive modeling for location, scale, and shape (GAMLSS) that facilitates the simulation of demographic covariates specific to the targeted patient populations. The goal was to optimize phase I dosing strategies and the likelihood of achieving target exposure and therapeutic effect. PMID:19847163

  10. [Effects of introduction of short peptides before carotid artery occlusion on behaviour and caspase-3 activity in the brain of old rats].

    Science.gov (United States)

    Mendzheritskiĭ, A M; Karantysh, G V; Ivonina, K O

    2011-01-01

    The comparative research of effect of Pinealon and Cortexin on behavior and activity of caspase-3 in a brain of old rats in a model of carotid arteries occlusion was conducted. It is shown that introduction of short peptides promotes a survival rate of the animals that have modeled occlusion of carotid arteries. Under Pinealon before occlusion of carotid arteries, behavioral dream has been increased and a position-finding behavior, a motivational behavior and a motor performance have been reduced. The rats that were introduced Cortexin before carotid arteries occlusion demonstrated the raise of behavioral dream time. At introduction of Pinealon activity of caspase-3 moderately raises in false-operated animals and in a model of occlusion of carotid arteries. PMID:21809624

  11. Short cationic lipopeptides as effective antibacterial agents: Design, physicochemical properties and biological evaluation.

    Science.gov (United States)

    Azmi, Fazren; Elliott, Alysha G; Marasini, Nirmal; Ramu, Soumya; Ziora, Zyta; Kavanagh, Angela M; Blaskovich, Mark A T; Cooper, Matthew A; Skwarczynski, Mariusz; Toth, Istvan

    2016-05-15

    The spread of drug-resistant bacteria has imparted a sense of urgency in the search for new antibiotics. In an effort to develop a new generation of antibacterial agents, we have designed de novo charged lipopeptides inspired by natural antimicrobial peptides. These short lipopeptides are composed of cationic lysine and hydrophobic lipoamino acids that replicate the amphiphilic properties of natural antimicrobial peptides. The resultant lipopeptides were found to self-assemble into nanoparticles. Some were effective against a variety of Gram-positive bacteria, including strains resistant to methicillin, daptomycin and/or vancomycin. The lipopeptides were not toxic to human kidney and liver cell lines and were highly resistant to tryptic degradation. Transmission electron microscopy analysis of bacteria cells treated with lipopeptide showed membrane-damage and lysis with extrusion of cytosolic contents. With such properties in mind, these lipopeptides have the potential to be developed as new antibacterial agents against drug-resistant Gram-positive bacteria. PMID:27048775

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. Short Bowel Patients Treated for Two Years with Glucagon-Like Peptide 2 (GLP-2: Compliance, Safety, and Effects on Quality of Life

    Directory of Open Access Journals (Sweden)

    P. B. Jeppesen

    2009-01-01

    Full Text Available Background and aims. Glucagon-like peptide 2 (GLP-2 has been shown to improve intestinal absorption in short bowel syndrome (SBS patients in a short-term study. This study describes safety, compliance, and changes in quality of life in 11 SBS patients at baseline, week 13, 26, and 52 during two 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. Results. The predominant adverse event was transient abdominal discomfort in 5 of 11 patients, but in 2, both suffering from Crohns disease, it progressed to abdominal pain and led to discontinuation of GLP-2 treatment. One had a fibrostenotic lesion electively resected at the jejuno-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<.01, the overall SIP score (10.3±8.9% versus 6.2±9.5%, P<.001, the mental component of the SF-36 (45±13% versus 53±11%, P<.05, and the overall IBDQ score (5.1±0.9 versus 5.4±0.9, P<.007 in the 8 patients completing the study. Conclusions. Long-term treatment with GLP-2 is feasible in SBS patients, although caution must be exercised in patients with a history of abdominal pain. Although conclusions cannot be made in a noncontrolled trial, the high reported compliance might reflect a high treatment satisfaction, where the clinical benefits of GLP-2 may outweigh the discomforts of injections.

  19. Amphiphilic silver particles for conductive inks with controlled wetting behavior

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Bok Yeop, E-mail: byahn@seas.harvard.edu [Wyss Institute for Biologically Inspired Engineering at Harvard University, Cambridge, MA 02138 (United States); Lewis, Jennifer A. [Wyss Institute for Biologically Inspired Engineering at Harvard University, Cambridge, MA 02138 (United States); Harvard School of Engineering and Applied Science, Cambridge, MA 02138 (United States)

    2014-12-15

    Silver inks find applications in printed electronics as conductive electrodes. Amphiphilic silver microparticles are prepared by modifying PAA-capped particles with functional amines via an amidation reaction. These modified silver particles can be dispersed in a wide variety of solvents ranging from water (ε = 80.4) to lipophilic alcohols (ε = 3–17) to yield conductive inks with tunable wettability. Using these inks, we have demonstrated aerosol jet printing of conductive silver patterns (36 μm wide, 1.2 μm thick) on Kapton. Electrical resistivity of 3.7 μΩ cm is obtained after thermal annealing at 225 °C for 5 min. Similar electrical resistivity (3.9 μΩ cm) is achieved after photonic annealing as short as 1 ms at 1.4 KV. - Highlights: • Synthesis of amphiphilic silver particles. • Surface modification of silver particles by amidation. • Dispersion, contact angle, surface tension of silver inks. • Aerosol jet printing of silver inks on polyimide. • Conductivity by thermal and photonical annealing.

  20. Amphiphilic silver particles for conductive inks with controlled wetting behavior

    International Nuclear Information System (INIS)

    Silver inks find applications in printed electronics as conductive electrodes. Amphiphilic silver microparticles are prepared by modifying PAA-capped particles with functional amines via an amidation reaction. These modified silver particles can be dispersed in a wide variety of solvents ranging from water (ε = 80.4) to lipophilic alcohols (ε = 3–17) to yield conductive inks with tunable wettability. Using these inks, we have demonstrated aerosol jet printing of conductive silver patterns (36 μm wide, 1.2 μm thick) on Kapton. Electrical resistivity of 3.7 μΩ cm is obtained after thermal annealing at 225 °C for 5 min. Similar electrical resistivity (3.9 μΩ cm) is achieved after photonic annealing as short as 1 ms at 1.4 KV. - Highlights: • Synthesis of amphiphilic silver particles. • Surface modification of silver particles by amidation. • Dispersion, contact angle, surface tension of silver inks. • Aerosol jet printing of silver inks on polyimide. • Conductivity by thermal and photonical annealing

  1. Novel Tripod Amphiphiles for Membrane Protein Analysis

    DEFF Research Database (Denmark)

    Chae, Pil Seok; Kruse, Andrew C; Gotfryd, Kamil; Rana, Rohini R; Cho, Kyung Ho; Rasmussen, Søren G F; Bae, Hyoung Eun; Chandra, Richa; Gether, Ulrik; Guan, Lan; Kobilka, Brian K; Loland, Claus J; Byrne, Bernadette; Gellman, Samuel H

    2013-01-01

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

  2. 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

  3. Bola-amphiphile self-assembly

    DEFF Research Database (Denmark)

    Svaneborg, Carsten

    2012-01-01

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

  4. Fluctuations and structure of amphiphilic films

    International Nuclear Information System (INIS)

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

  5. 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 ...

  6. 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

  7. Acute effects of continuous infusions of glucagon-like peptide (GLP)-1, GLP-2 and the combination (GLP-1+GLP-2) on intestinal absorption in short bowel syndrome (SBS) patients. A placebo-controlled study

    DEFF Research Database (Denmark)

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

    2013-01-01

    The ileocolonic brake is impaired in short bowel syndrome (SBS) patients with distal bowel resections. An attenuated meal-stimulated hormone secretion may cause gastric hypersecretion, rapid gastric and intestinal transit and a poor adaptation. Attempting to restore this ileocolonic brake, 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....

  8. 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...

  9. Solid lipid nanoparticles from amphiphilic calixpyrroles

    OpenAIRE

    Helttunen, Kaisa; Galán, Albano; Ballester, Pablo; Bergenholtz, Johan; Nissinen, Maija

    2016-01-01

    Hypothesis Macrocyclic amphiphiles form interesting self-assembling structures, including solid lipid nanoparticles, which have potential applications in drug encapsulation. Aryl-extended calixpyrroles, which act as anion binding hosts, are expected to form solid lipid nanoparticles, even though the alkyl chains have unusual perpendicular geometry with respect to the hydrophilic head group. The preparation conditions and the alkyl chain length should affect the size and stability of the p...

  10. 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 ...

  11. 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 ...

  12. 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

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

    Science.gov (United States)

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

    2015-03-12

    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. PMID:25737427

  14. 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.

  15. 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

  16. Molecular Dynamics of Peptide Folding at Aqueous Interfaces

    Science.gov (United States)

    Pohorille, Andrew; Chipot, Christophe; Chang, Sherwood (Technical Monitor)

    1997-01-01

    Even though most monomeric peptides are disordered in water they can adopt sequence-dependent, ordered structures, such as a-helices, at aqueous interfaces. This property is relevant to cellular signaling, membrane fusion, and the action of toxins and antibiotics. The mechanism of folding nonpolar peptides at the water-hexane interface was studied in the example of an 11-mer, of poly-L-leucine. Initially placed as a random coil on the water side of the interface, the peptide folded into an a-helix in 36 ns. Simultaneously, the peptide translocated into the hexane side of the interface. Folding was not sequential and involved a 3/10-helix as an intermediate. The folded peptide was either parallel to the interface or had its C-terminus exposed to water. An 11-mer, LQQLLQQLLQL, composed of leucine (L) and glutamine (G), was taken as a model amphiphilic peptide. It rapidly adopted an amphiphilic, disordered structure at the interface. Further folding proceeded through a series of amphiphilic intermediates.

  17. 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

  18. 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

  19. 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

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

    DEFF Research Database (Denmark)

    Chae, Pil Seok; Rana, Rohini R; Gotfryd, Kamil; Rasmussen, Søren G F; Kruse, Andrew C; Cho, Kyung Ho; Capaldi, Stefano; Carlsson, Emil; Kobilka, Brian; Loland, Claus J; Gether, Ulrik; Banerjee, Surajit; Byrne, Bernadette; Lee, John K; Gellman, Samuel H

    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...

  1. 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

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  3. 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; Pironi, L; Gabe, S M; Joly, F; Messing, B; Loth, S; Youssef, N N; Heinze, H; Berghöfer, P

    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......% while maintaining oral fluid intake constant; placebo-treated patients had reduced PS by 21%, but oral fluid intake increased accordingly. As effects of teduglutide on QoL are unknown, they were investigated here....

  4. 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; Brandt, C F; Hartmann, B; Holst, Jens Juul; Mortensen, P B; Jeppesen, P B

    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...... endogenous GLP-2 secretion, which may contribute to their rapid gastric emptying, gastric hypersecretion and poor intestinal adaptation, whereas SBS patients with preserved terminal ileum and colon, who have a constantly elevated GLP-2 secretion, seem to do better in these respects. This study compared...

  5. 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.

  6. 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.

  7. 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.

  8. Amphiphilic Polymer Micellar Disruption Based on Main-Chain Photodegradation.

    Science.gov (United States)

    Tian, Min; Cheng, Ruidong; Zhang, Jun; Liu, Zhaotie; Liu, Zhongwen; Jiang, Jinqiang

    2016-01-12

    The amphiphilic block copolymer poly(ethylene oxide)-b-poly(N,N'-dihydroxypyromellitimide-hexamethylene diisocyanate) (PEO-b-PNH) with photocleavable N-O urethanes has been prepared to investigate the photodegradation of the hydrophobic main chain and therefore the disruption of copolymer micelles. Measurements of absorption and emission spectra, optical transmittance, DLS analysis, and TEM observations were applied. It was shown that PEO-b-PNH could self-assemble into flower compound micelles in water. The photodegradation of the hydrophobic polyurethane within the micellar core upon irradiation with 365 nm light could be conveniently controlled by changing the irradiation intensity; furthermore, complete micellar disruption could be achieved when 42% of N-O urethanes were photocleaved. By using DOX as the hydrophobic guest, the drug release profile showed a linear leakage of DOX out of the swelling polymer micelles in the initial stage and thereafter a much more quick exponential decay of DOX precipitation because of the micellar disruption upon further irradiation. The diffusion experiment of the leaked DOX into buffer solution (pH 7.4) showed that the DOX leakage could be prominently accelerated by a very short time of 365 nm irradiation, indicating that the N-O photocleavage can serve as a "turn-on" switch for the release of DOX in aqueous media. PMID:26641733

  9. Novel amphiphilic networks for biological use

    Czech Academy of Sciences Publication Activity Database

    Toman, Luděk; Janata, Miroslav; Spěváček, Jiří; Sikora, Antonín; Pleštil, Josef; Michálek, Jiří; Dvořánková, B.; Vlček, Petr; Látalová, Petra; Masař, Bohumil

    Prague: Czech Society for New Materials and Technologies, 2005. Poster Session II. [European Congress on Advanced Materials and Processes. 5.9.2005-8.9.2005, Prague] R&D Projects: GA ČR GA203/04/1050 Keywords : polyisobutylene * poly(2-hydroxyethyl methacrylate) * amphiphilic networks Subject RIV: CD - Macromolecular Chemistry http://webdb.dgm.de/dgm_lit/prg/FMPro?-db=w%5fprogram&- format =prog%5fpaper%5fresults.htm&-lay=standard&TB=%3d%3d688&tgb%5fsymposium%5fund%5fnr=B14%20Engineering%20and%20Design%20of%20Biomedical%20Materials&-max=20&-skip=20&-token.0=688&-token.1=B14%20Engineering%20and%20Design%20of%20Biomedical%20Materials&-find=

  10. Cationic Antimicrobial Peptide Cytotoxicity

    OpenAIRE

    Laverty, Garry; Gilmore, Brendan

    2014-01-01

    Fluorescence microscopy serves as a valuable tool for assessing the structural integrity and viability of eukaryotic cells. Through the use of calcein AM and the DNA stain 4,6-diamidino-2 phenylindole (DAPI), cell viability and membrane integrity can be qualified. Our group has previously shown the ultra-short cationic antimicrobial peptide H-OOWW-NH2; the amphibian derived 27-mer peptide Maximin-4and the ultra-short lipopeptide C12-OOWW-NH2 to be effective against a range of bacterial biofil...

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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.

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

    International Nuclear Information System (INIS)

    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

  17. 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)].

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    Acute infusion of glucagon-like-peptide-1 (GLP-1) has potent effects on blood flow distribution through the microcirculation in healthy humans and rats. High fat diet induces impairments in insulin-mediated microvascular recruitment (MVR) and muscle glucose uptake, and here we examined whether this......-mediated glucose uptake in skeletal muscle by 90% (P<0.05) after 5 days HF diet but not after 8 weeks. The present study demonstrates that GLP-1 increases MVR in rat skeletal muscle and can reverse early stages of HF diet induced insulin resistance in vivo. This article is protected by copyright. All rights...

  19. 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...

  20. Understanding the Robust Physisorption between Bovine Serum Albumin and Amphiphilic Polymer Coated Nanoparticles.

    Science.gov (United States)

    Liu, Yushuang; Zhong, Ruibo; Zhang, Ping; Ma, Yuxing; Yun, Xiaoling; Gong, Pei; Wei, Jianmin; Zhao, Xinmin; Zhang, Feng

    2016-02-01

    The robust physisorption between nanoparticles (NPs) and proteins has attracted increasing attention due to the significance for both conjugation techniques and protein's corona formation at the bionano interface. In the present study, we first explored the possible binding sites of the bovine serum albumin (BSA) on amphiphilic polymer coated gold nanoparticles (AP-AuNPs). By using mass spectrometry, a 105-amino-acid peptide (12.2 kDa) is discovered as the possible "epitope" responsible for the robust physisorption between BSA and AP-AuNPs. Second, with the help of nanometal surface energy transfer (NSET) theory, we further found that the epitope peptide could insert at least 2.9 nm into the organic molecular layers of AP-AuNPs when the robust conjugates formed, which indicates how such a long epitope peptide can be accommodated by AP-AuNPs and resist protease's digestion. These findings might shed light on a new strategy for studying interactions between proteins and NPs, and further guide the rational design of NPs for safe and effective biomedical applications. PMID:26718324

  1. 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

  2. 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

  3. Peptide dendrimers

    Czech Academy of Sciences Publication Activity Database

    Niederhafner, Petr; Šebestík, Jaroslav; Ježek, Jan

    2005-01-01

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

  4. Interfacial adsorption and aggregation of amphiphilic proteins

    Science.gov (United States)

    Cheung, David

    2012-02-01

    The adsorption and aggregation on liquid interfaces of proteins is important in many biological contexts, such as the formation of aerial structures, immune response, and catalysis. Likewise the adsorption of proteins onto interfaces has applications in food technology, drug delivery, and in personal care products. As such there has been much interest in the study of a wide range of biomolecules at liquid interfaces. One class of proteins that has attracted particular attention are hydrophobins, small, fungal proteins with a distinct, amphiphilic surface structure. This makes these proteins highly surface active and they recently attracted much interest. In order to understand their potential applications a microscopic description of their interfacial and self-assembly is necessary and molecular simulation provides a powerful tool for providing this. In this presentation I will describe some recent work using coarse-grained molecular dynamics simulations to study the interfacial and aggregation behaviour of hydrophobins. Specifically this will present the calculation of their adsorption strength at oil-water and air-water interfaces, investigate the stability of hydrophobin aggregates in solution and their interaction with surfactants.

  5. 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

  6. Biodegradable copolymers carrying cell-adhesion peptide sequences.

    Science.gov (United States)

    Proks, Vladimír; Machová, Lud'ka; Popelka, Stepán; Rypácek, Frantisek

    2003-01-01

    Amphiphilic block copolymers are used to create bioactive surfaces on biodegradable polymer scaffolds for tissue engineering. Cell-selective biomaterials can be prepared using copolymers containing peptide sequences derived from extracellular-matrix proteins (ECM). Here we discuss alternative ways for preparation of amphiphilic block copolymers composed of hydrophobic polylactide (PLA) and hydrophilic poly(ethylene oxide) (PEO) blocks with cell-adhesion peptide sequences. Copolymers PLA-b-PEO were prepared by a living polymerisation of lactide in dioxane with tin(II)2-ethylhexanoate as a catalyst. The following approaches for incorporation of peptides into copolymers were elaborated. (a) First, a side-chain protected Gly-Arg-Gly-Asp-Ser-Gly (GRGDSG) peptide was prepared by solid-phase peptide synthesis (SPPS) and then coupled with delta-hydroxy-Z-amino-PEO in solution. In the second step, the PLA block was grafted to it via a controlled polymerisation of lactide initiated by the hydroxy end-groups of PEO in the side-chain-protected GRGDSG-PEO. Deprotection of the peptide yielded a GRGDSG-b-PEO-b-PLA copolymer, with the peptide attached through its C-end. (b) A protected GRGDSG peptide was built up on a polymer resin and coupled with Z-carboxy-PEO using a solid-phase approach. After cleavage of the delta-hydroxy-PEO-GRGDSG copolymer from the resin, polymerisation of lactide followed by deprotection of the peptide yielded a PLA-b-PEO-b-GRGDSG block copolymer, in which the peptide is linked through its N-terminus. PMID:12903721

  7. 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.

  8. 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.

  9. 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.

  10. 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)

  11. 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

  12. 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

  13. 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

  14. Surface, Interfacial and Tribological Properties of Cereal-based Amphiphiles

    Science.gov (United States)

    Starch, protein and oil are the major components of most cereals such as corn and soybean. These components, with or without further chemical modification, display a number of important amphiphilic characteristics that are of interest in a number of applications. Cereal-based oils have polar compo...

  15. Supramolecular barrels from amphiphilic rigid-flexible macrocycles

    Science.gov (United States)

    Yang, Won-Young; Ahn, Jong-Hyun; Yoo, Yong-Sik; Oh, Nam-Keun; Lee, Myongsoo

    2005-05-01

    Precise control of supramolecular objects requires the rational design of molecular components, because the information determining their specific assembly should be encoded in their molecular architecture. In this context, diverse self-assembling molecules including liquid crystals, dendrimers, block copolymers, hydrogen-bonded complexes and rigid macrocycles are being created as a means of manipulating supramolecular structure. Incorporation of a stiff rod-like building block into an amphiphilic molecular architecture leads to another class of self-assembling molecules. Aggregation of rod building blocks can generate various nanoscale objects including bundles, ribbons, tubules and vesicles, depending on the molecular structure and/or the presence of a selective solvent. We present here an unusual example of supramolecular barrels in the solid and in aqueous solution, based on the self-assembly of amphiphilic rigid-flexible macrocycles driven by non-covalent interactions. Preliminary experiments show that these amphiphilic macrocycles are membrane-active. The amphiphilic macrocycles might thus lead to an excellent model system for exploring biological processes in supramolecular materials.

  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. 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.

  18. 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

  19. 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

  20. 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

  1. 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

  2. Alanine scan and (2)H NMR analysis of the membrane-active peptide BP100 point to a distinct carpet mechanism of action.

    Science.gov (United States)

    Zamora-Carreras, Héctor; Strandberg, Erik; Mühlhäuser, Philipp; Bürck, Jochen; Wadhwani, Parvesh; Jiménez, M Ángeles; Bruix, Marta; Ulrich, Anne S

    2016-06-01

    The short membrane-active peptide BP100 [KKLFKKILKYL-NH2] is known as an effective antimicrobial and cell penetrating agent. For a functional alanine scan each of the 11 amino acids was replaced with deuterated Ala-d3, one at a time. MIC assays showed that a substitution of Lys did not affect the antimicrobial activity, but it decreased when a hydrophobic residue was replaced. In most cases, a reduction in hydrophobicity led to a decrease in hemolysis, and some peptide analogues had an improved therapeutic index. Circular dichroism showed that BP100 folds as an amphiphilic α-helix in a bilayer. Its alignment was determined from (2)H NMR in oriented membranes of different composition. The azimuthal rotation angle was the same under all conditions, but the average helix tilt angle and the dynamical behavior of the peptide varied in a systematic manner. In POPC/POPG bilayers, with a negative spontaneous curvature, the peptide was found to lie flat on the bilayer surface, and with little wobble. In DMPC/DMPG, with a positive spontaneous curvature, BP100 at higher concentrations became tilted obliquely into the membrane, with the uncharged C-terminus inserted more deeply into the lipid bilayer, experiencing significant fluctuations in tilt angle. In DMPC/DMPG/lyso-MPC, with a pronounced positive spontaneous curvature, the helix tilted even further and became even more mobile. The 11-mer BP100 is obviously too short to form transmembrane pores. We conclude that BP100 operates via a carpet mechanism, whereby the C-terminus gets inserted into the hydrophobic core of the bilayer, which leads to membrane perturbation and induces transient permeability. PMID:26975251

  3. 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.

  4. 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

  5. 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

  6. 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

  7. 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.

  8. 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

  9. Molecular dynamics simulation of micellar shape transition in amphiphilic solutions

    International Nuclear Information System (INIS)

    The micellar shape transition in amphiphilic solutions is studied by coarse-grained molecular dynamics simulations of rigid amphiphilic molecules with explicit solvent molecules. Our simulations show that the dominant micellar shape changes from disc to cylinder, and then to sphere as the hydrophilic interaction increases. We find that, as the hydrophilic interaction increases, the potential energy decreases monotonically even during the micellar shape transition, whereas the slope of the potential energy decreases in a stepwise manner in relation to the micellar shape transition. We also ascertained that there exists a wide coexistence region in the intensity of the hydrophilic interaction between a cylinder and a sphere, whereas the coexistence region between a cylinder and a disc is very narrow. (author)

  10. 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

  11. 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.

  12. 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...

  13. Hydration of an amphiphilic excipient, Gelucire 44/14

    OpenAIRE

    Svensson, Anna; Neves, Carole; Cabane, Bernard

    2004-01-01

    The hydration behavior of an amphiphilic excipient, Gelucire 44/14, has been investigated. Two types of hydration processes were studied: one with increasing humidity to investigate the conditions during storage, and one with increasing water contents to study the behavior during dissolution. In addition, the main components of the excipient were investigated separately. These were polyethylene glycol (PEG), PEG monolaurate and PEG dilaurate (PEG esters), trilaurin (glyceride) and glycerol. T...

  14. 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...

  15. 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...

  16. 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...

  17. 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

  18. 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...

  19. 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

  20. 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

  1. 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.

  2. 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.

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

    DEFF Research Database (Denmark)

    Nørgaard, K.; Weygand, M.J.; Kjær, K.; Brust, M.; Bjørnholm, T.

    2004-01-01

    A series of ligand stabilized gold nanoparticles with diameters close to 3 nm were studied as Langmuir monolayers at the air/water interface by synchrotron X-ray diffraction and reflectivity. Alkylthiols with different length and/or terminal functional group (hydrophilic or hydrophobic) were...... environmental responsiveness, as they adapt to an amphiphilic distribution of ligands around the gold core when spread at the water surface. Likewise nanoparticles of mixed long and short alkyl chains respond to lateral pressure by adopting a structure where the short alkyl chains determine the in-plane nearest...

  4. 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...

  5. 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

  6. 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

  7. From Stealthy Polymersomes and Filomicelles to “Self” Peptide-Nanoparticles for Cancer Therapy

    OpenAIRE

    Oltra, Núria Sancho; Nair, Praful; Discher, Dennis E.

    2014-01-01

    Polymersome vesicles and wormlike filomicelles self-assembled with amphiphilic, degradable block copolymers have recently shown promise in application to cancer therapy. In the case of filomicelles, dense, hydrophilic brushes of poly(ethylene glycol) on these nanoparticles combine with flexibility to nonspecifically delay clearance by phagocytes in vivo, which has motivated the development of “self” peptides that inhibit nanoparticle clearance through specific interactions. Delayed clearance,...

  8. 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

  9. 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

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    this work, we have investigated the diffusion properties of Pindolol, Quinine and Timolol maleate from RADA16 in PBS and in BSS-PLUS at 37°C. A sustained, controlled, reproducible and efficient drug release has been detected for all the systems, which allows to understand the dependence of release...

  11. 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

  12. 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

  13. Synthesis nad properties of amphiphilic block copolymers containing poly 5-vinyltetrazoline or methyl-4-vinylpyridinium iodide

    Czech Academy of Sciences Publication Activity Database

    Gromadzki, D.; Janata, Miroslav; Lokaj, Jan; Štěpánek, Petr

    Arcachon: European Science Foundation Collaborative Research, 2005. P2. [Self-Assembled Structures of Amphiphilic Ionic Copolymers in Solutions and Interfaces. 11.5.2005-14.5.2005, Arcachon] Institutional research plan: CEZ:AV0Z40500505 Keywords : amphiphilic block copolymers Subject RIV: CD - Macromolecular Chemistry

  14. 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

    vesicles were shown to be more stable than those formed by pure fatty acids. Those containing bola-amphiphile even showed encapsulation of a small hydrophilic solute (8-hydroxypyrene-1,3,6-trisulfonic-acid) suggesting a denser packing of the amphiphiles. Compression and kinetics analysis of monolayers...

  15. 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...

  16. 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.

  17. Liquid-solid extraction of metallic cations by cationic amphiphiles

    International Nuclear Information System (INIS)

    In the field of selective metal ion separation, liquid-liquid extraction is usually conducted through an emulsion mixing of hydrophobic complexants dispersed in an organic phase and acidic water containing the ionic species. Recently, it has been shown that amphiphilic complexants could influence strongly extraction efficiency by enhancing the interfacial interaction between the metal ion in the aqueous and the complexant in the organic phase. Moreover, these amphiphiles can also substitute the organic phase if an appropriate aliphatic chain is chosen. The dispersion of such amphiphilic complexants in an aqueous solution of salt mixtures is not only attractive for studying specific interactions but also to better the understanding of complex formation in aqueous solution of multivalent metal ions, such as lanthanides and actinides. This understanding is of potential interest for a broad range of industries including purification of rare earth metals and pollute treatment e.g. of fission byproducts. This principle can also be applied to liquid-solid extraction, where the final state of the separation is a solid phase containing the selectively extracted ions. Indeed, a novel solid-liquid extraction method exploits the selective precipitation of metal ions from an aqueous salt mixture using a cationic surfactant, below its Krafft point (temperature below which the long aliphatic chains of surfactant crystallize). This technique has been proven to be highly efficient for the separation of actinides and heavy metal using long chain ammonium or pyridinium amphiphiles. The most important point in this process is the recognition of cationic metal ions by cationic surfactants. By computing the free energy of the polar head group per micelle as a function of the different counter-anions, we have demonstrated for the first time that different interactions exist between the micellar surface and the ions. These interactions depend on the nature of the cation but also on

  18. 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

  19. 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

  20. 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...

  1. 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.

  2. Selection of Genetic engineering peptide ligands for TNF receptor imaging

    International Nuclear Information System (INIS)

    Objective: To screen the peptide ligands of TNF receptor from phage 6-mer peptide library with the purpose of developing new peptides radiopharmaceuticals for TNF receptor imaging. Methods: The soluble protein of TNF receptor I (sTNFR I) was used to screen the TNF-specific epitopes from phage 6-mer peptide library. After four rounds of affinity screening, the peptides displayed on the selected phage were directly subjected to ELISA to determine their immunological activity to sTNFR. The amino acid sequences of the peptides with highest immunological activity were deduced through DNA sequencing. And their conserved sequences were further determined. Results: Peptides sequences mimicking TNF-specific epitopes were obtained. Conclusion: The short peptides sequences mimicking TNF -specific epitopes were successfully acquired. The method which was established in the present study may provide a feasible way in peptides radiopharmaceuticals development for TNF receptor imaging. (authors)

  3. 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.

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

    International Nuclear Information System (INIS)

    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

  5. Conformational changes of phospholipid headgroups induced by a cationic integral membrane peptide as seen by deuterium magnetic resonance

    International Nuclear Information System (INIS)

    Deuterium nuclear magnetic resonance (2H NMR) was used to study the interaction of a cationic amphiphilic peptide with pure DMPC membranes and with mixed bilayers of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylserine (DMPS). The choline and serine headgroups were selectively deuteriated at the alpha and beta positions. The amphiphilic peptide, with 20 leucine residues in the hydrophobic core and two cationic hydrophilic lysine residues at each end, spanned the lipid bilayer. Although 2H NMR experiments using DMPC with perdeuteriated fatty acyl chains showed that the average order parameter of the hydrophobic region was not significantly modified by the incorporation of the amphiphilic peptide, for either DMPC or DMPC/DMPS (5:1) bilayers, large perturbations of the quadrupolar splittings of the choline and serine headgroups were observed. The results obtained with the DMPC headgroup suggest that the incorporation of the cationic peptide in both DMPC and DMPC/DMPS (5:1) bilayers leads to a structural perturbation directly related to the net charge on the membrane surface. The magnitude of the observed effect seems to be similar to those observed previously with other cationic molecules. Two of the three quadrupolar splittings of the PS headgroup exhibited large variations in the presence of the amphiphilic peptide, while the third one remained unchanged. Our data have led us to propose a model describing the influence of membrane surface charges on headgroup conformation. In this model, the surface charge is represented as a uniform charge distribution. The electric field due to the charges produces a torque which rotates the polar headgroups

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. 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....

  11. 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 ...

  12. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-11-15

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

  14. 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

  15. 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...

  16. 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

  17. 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

  18. 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...

  19. Surfactant Behavior of Amphiphilic Polymer-Tethered Nanoparticles.

    Science.gov (United States)

    Zhang, Yue; Zhao, Hanying

    2016-04-19

    In recent years, an emerging research area has been the surfactant behavior of polymer-tethered nanoparticles. In this feature article, we have provided a general introduction to the synthesis, self-assembly, and interfacial activity of polymer-tethered inorganic nanoparticles, polymer-tethered organic nanoparticles, and polymer-tethered natural nanoparticles. In addition, applications of the polymer-tethered nanoparticles in colloidal and materials science are briefly reviewed. All research demonstrates that amphiphilic polymer-tethered nanoparticles exhibit surfactant behavior and can be used as elemental building blocks for the fabrication of advanced structures by the self-assembly approach. The polymer-tethered nanoparticles provide new opportunities to engineer materials and biomaterials possessing specific functionality and physical properties. PMID:27018567

  20. Rational Design of Pathogen-Mimicking Amphiphilic Materials as Nanoadjuvants

    Science.gov (United States)

    Ulery, Bret D.; Petersen, Latrisha K.; Phanse, Yashdeep; Kong, Chang Sun; Broderick, Scott R.; Kumar, Devender; Ramer-Tait, Amanda E.; Carrillo-Conde, Brenda; Rajan, Krishna; Wannemuehler, Michael J.; Bellaire, Bryan H.; Metzger, Dennis W.; Narasimhan, Balaji

    2011-12-01

    An opportunity exists today for cross-cutting research utilizing advances in materials science, immunology, microbial pathogenesis, and computational analysis to effectively design the next generation of adjuvants and vaccines. This study integrates these advances into a bottom-up approach for the molecular design of nanoadjuvants capable of mimicking the immune response induced by a natural infection but without the toxic side effects. Biodegradable amphiphilic polyanhydrides possess the unique ability to mimic pathogens and pathogen associated molecular patterns with respect to persisting within and activating immune cells, respectively. The molecular properties responsible for the pathogen-mimicking abilities of these materials have been identified. The value of using polyanhydride nanovaccines was demonstrated by the induction of long-lived protection against a lethal challenge of Yersinia pestis following a single administration ten months earlier. This approach has the tantalizing potential to catalyze the development of next generation vaccines against diseases caused by emerging and re-emerging pathogens.

  1. 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)

  2. 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

  3. 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

  4. 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.

  5. 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.

  6. Non-Surface Activity of Cationic Amphiphilic Diblock Copolymers

    International Nuclear Information System (INIS)

    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.

  7. Transformable Peptide Nanocarriers for Expeditious Drug Release and Effective Cancer Therapy via Cancer‐Associated Fibroblast Activation

    OpenAIRE

    Ji, Tianjiao; Zhao, Ying; Ding, Yanping; Wang, Jing; Zhao, Ruifang; Lang, Jiayan; Qin, Hao; Liu, Xiaoman; Shi, Jian; Tao, Ning; Qin, Zhihai; Nie, Guangjun; Zhao, Yuliang

    2015-01-01

    Abstract A novel cleavable amphiphilic peptide (CAP) was designed to be specifically responsive to fibroblast activation protein‐α (FAP‐α), a protease specifically expressed on the surface of cancer‐associated fibroblasts. The CAP self‐assembled into fiber‐like nanostructures in solution, while the presence of hydrophobic chemotherapeutic drugs readily transformed the assemblies into drug‐loaded spherical nanoparticles. The disassembly of these nanoparticles (CAP‐NPs) upon FAP‐α cleavage resu...

  8. Controlling morphology and dynamics of nano-scale assemblies of amphiphilic copolymers in aqueous environment

    Czech Academy of Sciences Publication Activity Database

    Borisova, O. V.; Billon, L.; Grassl, B.; Štěpánek, Petr; Bakaeva, Zulfiya; Zaremski, M.; Zhulina, E. B.; Borisov, O. V.

    Pisa : European Polymer Federation, 2013. O3-7. [European Polymer Congress - EPF 2013. 16.06.2013-21.06.2013, Pisa] Institutional support: RVO:61389013 Keywords : nanoparticles * amphiphilic copolymers Subject RIV: CD - Macromolecular Chemistry

  9. 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...... amphiphiles on the early Earth seems reasonably well-documented either by exo-terrestrial delivery or endogeneous syntheses, a fact that singles them out as potential building blocks of primitive membranes. These studies have highlighted two important aspects of the self-assembly of single chain amphiphiles......: the medium composition in terms of ionic strengths and the medium physical parameters, such as temperature, significantly influence the formation of structures, as well as their subsequent stability. In addition, membranes composed of a single amphiphile type seem to be implausible as no potential...

  10. 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

  11. 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.

  12. Human peptide transporters

    DEFF Research Database (Denmark)

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

    2002-01-01

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

  13. 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

  14. 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. PMID:26440047

  15. 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

  16. 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.

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

    International Nuclear Information System (INIS)

    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, 1H NMR, 13C 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

  18. 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.

  19. 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...

  20. Cycloaddition in peptides for high-capacity optical storage

    DEFF Research Database (Denmark)

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

    2006-01-01

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

  1. Peptide-Carrier Conjugation

    DEFF Research Database (Denmark)

    Hansen, Paul Robert

    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.......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....

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

    Science.gov (United States)

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

    2014-09-22

    Nanofibrillated cellulose (NFC) and hemicelluloses have shown to be highly promising renewable components both as barrier materials and in novel biocomposites. However, the hydrophilic nature of these materials restricts their use in some applications. In this work, the usability of modified O-acetyl galactoglucomannan (GGM) for modification of NFC surface properties was studied. Four GGM-block-structured, amphiphilic derivatives were synthesized using either fatty acids or polydimethylsiloxane as hydrophobic tails. The adsorption of these GGM derivatives was consecutively examined in aqueous solution using a quartz crystal microbalance with dissipation monitoring (QCM-D). It was found that the hydrophobic tails did not hinder adsorption of the GGM derivatives to cellulose, which was concluded to be due to the presence of the native GGM-block with high affinity to cellulose. The layer properties of the adsorbed block-co-polymers were discussed and evaluated. Self-standing NFC films were further prepared and coated with the GGM derivatives and the effect of the surface modification on wetting properties and oxygen permeability (OP) of the modified films was assessed. PMID:24906743

  3. 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

  4. 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.

  5. Membrane deformation controlled by monolayer composition of embedded amphiphilic nanoparticles

    Science.gov (United States)

    van Lehn, Reid; Alexander-Katz, Alfredo

    2014-03-01

    In recent work, we have shown that charged, amphiphilic nanoparticles (NPs) can spontaneously insert into lipid bilayers, embedding the NP in a conformation resembling a transmembrane protein. Many embedded membrane proteins exert an influence on surrounding lipids that lead to deformation and membrane-mediated interactions that may be essential for function. Similarly, embedded NPs will also induce membrane deformations related to the same physicochemical forces. Unlike many transmembrane proteins, however, the highly charged NPs may exert preferential interactions on surrounding lipid head groups. In this work, we use atomistic molecular dynamics simulations to show that the membrane around embedded particles may experience local thinning, head group reorientation, and an increase in lipid density depending on the size and surface composition of the NP. We quantify the extent of these deformations and illustrate the complex interplay between lipid tail group and head group interactions that go beyond pure thickness deformations that may be expected from coarse-grained or continuum models. This work thus suggests guidelines for the design of particles that spontaneously partition into lipid bilayers and influence local membrane mechanical properties in a targeted manner.

  6. 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

  7. 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

  8. 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.

  9. Highly Branched Pentasaccharide-Bearing Amphiphiles for Membrane Protein Studies.

    Science.gov (United States)

    Ehsan, Muhammad; Du, Yang; Scull, Nicola J; Tikhonova, Elena; Tarrasch, Jeffrey; Mortensen, Jonas S; Loland, Claus J; Skiniotis, Georgios; Guan, Lan; Byrne, Bernadette; Kobilka, Brian K; Chae, Pil Seok

    2016-03-23

    Detergents are essential tools for membrane protein manipulation. Micelles formed by detergent molecules have the ability to encapsulate the hydrophobic domains of membrane proteins. The resulting protein-detergent complexes (PDCs) are compatible with the polar environments of aqueous media, making structural and functional analysis feasible. Although a number of novel agents have been developed to overcome the limitations of conventional detergents, most have traditional head groups such as glucoside or maltoside. In this study, we introduce a class of amphiphiles, the PSA/Es with a novel highly branched pentasaccharide hydrophilic group. The PSA/Es conferred markedly increased stability to a diverse range of membrane proteins compared to conventional detergents, indicating a positive role for the new hydrophilic group in maintaining the native protein integrity. In addition, PDCs formed by PSA/Es were smaller and more suitable for electron microscopic analysis than those formed by DDM, indicating that the new agents have significant potential for the structure-function studies of membrane proteins. PMID:26966956

  10. 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.

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. 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

  17. Water-inducing molecular self-assembly of amphiphilic molecules into nanofibers

    International Nuclear Information System (INIS)

    Graphical abstract: TPDP nanofibers with smooth surfaces can be obtained by reprecipitation method using ethanol as good solvent and water as poor solvent. In the self-assembly process, during the water adding to the amphiphilic molecules’ saturated solution, the amphiphilic molecules firstly assembled into needle-like small rods. With an increase in the self-assembled time, a large number of the nanofibers are produced. The assembly behavior was revealed in the course of direct in situ monitoring of its growth with optical microscopy. Highlights: ► 2,3,6,7-Tetramethoxy-9,10-di(4-pyridyl)-9,10-dihydroanthracen (TPDP) was synthesized. ► TPDP nanofibers can be obtained by reprecipitation method. ► The assembly behavior was revealed in situ monitoring with optical microscopy. -- Abstract: We present investigations on the microcosmic self-assembly process of new synthesized amphiphilic TPDP molecules. It can be seen that pure TPDP nanofibers with smooth surfaces can be obtained by reprecipitation method using ethanol as good solvent and water as poor solvent. In the self-assembly process, during the water adding to the amphiphilic molecules’ saturated solution, the amphiphilic molecules firstly assembled into needle-like small rods. With an increase in the self-assembled time, a large number of the nanofibers are produced. The assembly behavior was revealed in the course of direct in situ monitoring of its growth with optical microscopy. Field emission scanning electron microscopy was adopted to characterize the morphologies of the products.

  18. 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...

  19. Peptider holder krabben rask

    DEFF Research Database (Denmark)

    Buchmann, Kurt

    Antimikrobielle Peptider har hos mere primitive dyr en vigtig funktion i organismernes immunforsvar Udgivelsesdato: 1. februar......Antimikrobielle Peptider har hos mere primitive dyr en vigtig funktion i organismernes immunforsvar Udgivelsesdato: 1. februar...

  20. 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....

  1. 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....

  2. 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....

  3. 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....

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. Maltose-neopentyl glycol (MNG) amphiphiles for solubilization, stabilization and crystallization of membrane proteins

    DEFF Research Database (Denmark)

    Chae, Pil Seok; Rasmussen, Søren G F; Rana, Rohini R; Gotfryd, Kamil; Chandra, Richa; Goren, Michael A; Kruse, Andrew C; Nurva, Shailika; Løland, Claus Juul; Pierre, Yves; Drew, David; Popot, Jean-Luc; Picot, Daniel; Fox, Brian G; Guan, Lan; Gether, Ulrik; Byrne, Bernadette; Kobilka, Brian; Gellman, Samuel H

    2010-01-01

    The understanding of integral membrane protein (IMP) structure and function is hampered by the difficulty of handling these proteins. Aqueous solubilization, necessary for many types of biophysical analysis, generally requires a detergent to shield the large lipophilic surfaces of native IMPs. Many...... family show favorable behavior relative to conventional detergents, as manifested in multiple membrane protein systems, leading to enhanced structural stability and successful crystallization. MNG amphiphiles are promising tools for membrane protein science because of the ease with which they may be...... proteins remain difficult to study owing to a lack of suitable detergents. We introduce a class of amphiphiles, each built around a central quaternary carbon atom derived from neopentyl glycol, with hydrophilic groups derived from maltose. Representatives of this maltose-neopentyl glycol (MNG) amphiphile...

  10. Mixtures of ions and amphiphilic molecules in slit-like pores: A density functional approach

    Energy Technology Data Exchange (ETDEWEB)

    Pizio, O., E-mail: pizio@unam.mx [Instituto de Química, Universidad Nacional Autonoma de México, Circuito Exterior, Ciudad Universitaria, 04510 México, D. F. (Mexico); Rżysko, W., E-mail: wojtekrzysko@gmail.com; Sokołowski, S., E-mail: stefan.sokolowski@gmail.com [Department for the Modeling of Physico-Chemical Processes, Maria Curie-Skłodowska University, 20-031 Lublin (Poland); Sokołowska, Z., E-mail: sokolows@ipan.lublin.pl [Institute of Agrophysics, Polish Academy of Sciences, Doś wiadczalna 4, 20-290 Lublin (Poland)

    2015-04-28

    We investigate microscopic structure and thermodynamic properties of a mixture that contains amphiphilic molecules and charged hard spheres confined in slit-like pores with uncharged hard walls. The model and the density functional approach are the same as described in details in our previous work [Pizio et al., J. Chem. Phys. 140, 174706 (2014)]. Our principal focus is in exploring the effects brought by the presence of ions on the structure of confined amphiphilic particles. We have found that for some cases of anisotropic interactions, the change of the structure of confined fluids occurs via the first-order transitions. Moreover, if anions and cations are attracted by different hemispheres of amphiphiles, a charge at the walls appears at the zero value of the wall electrostatic potential. For a given thermodynamic state, this charge is an oscillating function of the pore width.

  11. 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

    predicted from measurements of isolated changes in such properties. Thus, the bilayer contribution to the promiscuous regulation of membrane proteins by drugs and other amphiphiles remains unknown. To overcome this problem, we use gramicidin A (gA) channels as molecular force probes to measure the net...... altering the energetic cost (Delta G(bilayer)) of bilayer deformations associated with protein conformational changes that involve the protein-bilayer interface. But amphiphiles have complex effects on the physical properties of lipid bilayers, meaning that the net change in Delta G(bilayer) cannot be......-dependent sodium channels in living cells. The use of gA channels as molecular force probes provides a tool for quantitative, predictive studies of bilayer-mediated regulation of membrane protein function by amphiphiles....

  12. 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

  13. Nanoaggregates of biodegradable amphiphilic random polycations for delivering water-insoluble drugs.

    Science.gov (United States)

    Nottelet, Benjamin; Patterer, Manuela; François, Benjamin; Schott, Marc-Alexandre; Domurado, Martine; Garric, Xavier; Domurado, Dominique; Coudane, Jean

    2012-05-14

    Cationic amphiphilic random copolyesters were obtained by copolymerization of 5-Z-amino-δ-valerolactone and ε-caprolactone. The amino content of the final copolymers was controlled by the polymerization feed ratio and was in the range 10 to 100%. Copolymers solubility and aggregation behavior was assessed by conductometric and zeta potential analyses. A critical aggregation concentration of ca. 0.05% (w/v) was found for all water-soluble copolymers that formed nanoaggregates. Two populations were found to be present in equilibrium with hydrodynamic diameters in the range of 30-50 and 100-250 nm. The capacity to use the amphiphilic and cationic character of the nanoaggregates to encapsulate highly hydrophobic compounds was further investigated. Finally, copolymers hemo- and cytocompatibility were evaluated by hemagglutination, hemolysis, and cells proliferation tests. The results showed that the proposed cationic amphiphilic random copolyesters are biocompatible. PMID:22458377

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

    International Nuclear Information System (INIS)

    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

  15. 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.

  16. 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...

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

    Science.gov (United States)

    Loo, Yihua; Hauser, Charlotte A E

    2016-02-01

    Three-dimensional (3D) bioprinting is a disruptive technology for creating organotypic constructs for high-throughput screening and regenerative medicine. One major challenge is the lack of suitable bioinks. Short synthetic self-assembling peptides are ideal candidates. Several classes of peptides self-assemble into nanofibrous hydrogels resembling the native extracellular matrix. This is a conducive microenvironment for maintaining cell survival and physiological function. Many peptides also demonstrate stimuli-responsive gelation and tuneable mechanical properties, which facilitates extrusion before dispensing and maintains the shape fidelity of the printed construct in aqueous media. The inherent biocompatibility and biodegradability bodes well for in vivo applications as implantable tissues and drug delivery matrices, while their short length and ease of functionalization facilitates synthesis and customization. By applying self-assembling peptide inks to bioprinting, the dynamic complexity of biological tissue can be recreated, thereby advancing current biomedical applications of peptide hydrogel scaffolds. PMID:26694103

  18. 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

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

    DEFF Research Database (Denmark)

    Javakhishvili, Irakli; Hvilsted, Søren

    2008-01-01

    Amphiphilic poly(c-caprolactone)-b-poly(acrylic acid) (HS-PCL-b-PAA) bearing thiol functionality at the PCL terminal has been synthesized by a combination of ring-opening polymerization (ROP) of c-caprolactone (c-CL), esterification of hydroxy chain end with protected mercaptoacetic acid, subsequ......Amphiphilic poly(c-caprolactone)-b-poly(acrylic acid) (HS-PCL-b-PAA) bearing thiol functionality at the PCL terminal has been synthesized by a combination of ring-opening polymerization (ROP) of c-caprolactone (c-CL), esterification of hydroxy chain end with protected mercaptoacetic acid...

  20. 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

    International Nuclear Information System (INIS)

    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.

  1. 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.

  2. 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 ...

  3. [Plant signaling peptides. Cysteine-rich peptides].

    Science.gov (United States)

    Ostrowski, Maciej; Kowalczyk, Stanisław

    2015-01-01

    Recent bioinformatic and genetic analyses of several model plant genomes have revealed the existence of a highly abundant group of signaling peptides that are defined as cysteine-rich peptides (CRPs). CRPs are usually in size between 50 and 90 amino acid residues, they are positively charged, and they contain 4-16 cysteine residues that are important for the correct conformational folding. Despite the structural differences among CRP classes, members from each class have striking similarities in their molecular properties and function. The present review presents the recent progress in research on signaling peptides from several families including: EPF/EPFL, SP11/SCR, PrsS, RALF, LURE, and some other peptides belonging to CRP group. There is convincing evidence indicating multiple roles for these CRPs as signaling molecules during the plant life cycle, ranging from stomata development and patterning, self-incompatibility, pollen tube growth and guidance, reproductive processes, and nodule formation. PMID:26281357

  4. 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

  5. A kinked antimicrobial peptide from Bombina maxima. II. Behavior in phospholipid bilayers.

    Science.gov (United States)

    Heinzmann, Ralf; Grage, Stephan L; Schalck, Constantin; Bürck, Jochen; Bánóczi, Zoltán; Toke, Orsolya; Ulrich, Anne S

    2011-04-01

    The preceding contribution by Toke et al. has studied the structure of the cationic antimicrobial peptide maximin-4 in detergent micelles and in organic solvent, revealing a different kink angle and side-chain interactions in the two different environments. Here, we have examined the same peptide in lipid bilayers using oriented circular dichroism (OCD) and solid-state (15)N nuclear magnetic resonance (NMR) in aligned samples. OCD showed that maximin-4 is helical and adopts an oblique alignment in the membrane, and lacks the characteristic realignment response that is often observed for amphipathic α-helical peptides at a peptide:lipid ratio between 1:100 and 1:20. Solid-state (15)N-NMR experiments suggest that maximin-4 also remains unaffected by lipid charge and temperature. Analyzing (15)N labels in positions Ala12, Ala13, and Leu14, an oblique tilt angle of the N-terminal helix of ~130° relative to the membrane normal was found, in good agreement with the amphiphilic profile of this segment. An additional constraint at Ala22 in the C-terminal segment is found to be compatible with a continuous α-helix, but unfavorable side-chain interactions make this solution unlikely. Instead, a kink at Gly16 seems fully compatible with all known constraints and with the biophysical expectations in the membrane-bound state, given the liquid-state NMR structures. It thus seems that the flexible kink in maximin-4 allows the two helical segments to adjust to the local environment. The irregular amphiphilic profile and the resulting versatility in shape might explain why maximin-4 lacks the realignment response that has been characteristically observed for many related frog peptides forming straight amphipathic α-helices. PMID:21312034

  6. 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

  7. 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

  8. 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.

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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)

  14. 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

  15. 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.

  16. Photostability of quantum dots with amphiphilic polymer-based passivation strategies

    International Nuclear Information System (INIS)

    Quantum dots (QDs) have many appealing properties for biological fluorescence imaging, but exhibit photostabilities that are dependent upon surface passivation to minimize susceptibility to oxygen and light. Here, through spectroscopy and imaging techniques, we compare the photostability of micelle-encapsulated QDs with QDs passivated with either crosslinked amphiphilic polymers or crosslink-free amphiphilic polymers. Both crosslinked and crosslink-free amphiphilic polymer passivation strategies produced QDs with high photoluminescence stability for exposure to light under ambient conditions. In contrast, micelle encapsulation resulted in QDs with photoluminescence emission levels that were highly sensitive to both light exposure and oxygen, exhibiting a reduction of up to 70% in photoluminescence intensity within twenty minutes of exposure. With the addition of reducing agents, the photoluminescence level of the micelle-encapsulated QDs was significantly stabilized. We conclude that amphiphilic polymers provide coatings with considerably higher integrity and stability than micelle encapsulation, reducing the QDs' sensitivities to oxygen and light, both of which are relevant factors in biological imaging applications

  17. 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...

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

    International Nuclear Information System (INIS)

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

  19. Stimuli-responsive nano-structures of amphiphilic ionic block- and gradient copolymers

    Czech Academy of Sciences Publication Activity Database

    Borisov, O.; Billon, L.; Borisova, O.; Štěpánek, Petr; Bakaeva, Zulfiya; Zhulina, E.

    Prague : Institute of Macromolecular Chemistry AS CR, 2014. s. 179. ISBN 978-80-85009-80-4. [Frontiers of Polymer Colloids: From Synthesis to Macro-Scale and Nano-Scale Applications. Prague Meeting on Macromolecules /78./. 20.07.2014-24.07.2014, Prague] Institutional support: RVO:61389013 Keywords : amphiphilic ionic copolymers * gradient copolymers Subject RIV: CD - Macromolecular Chemistry

  20. 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; Hvilsted, Søren; Lee, Seunghwan

    2014-01-01

    Amphiphilic anionic and cationic graft copolymers possessing poly(2-hydroxyethyl methacrylate) (PHEMA) backbone and poly(methacrylic acid), poly(2-methoxyethyl acrylate-co-methacrylic acid), and poly(2-methoxyethyl acrylate-co-2-(dimethylamino)ethyl methacrylate) grafts are constructed by merging...

  1. 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...

  2. 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 ...

  3. 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

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

    OpenAIRE

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

    2015-01-01

    Silicones with superior protein resistance were produced by bulk-modification with poly(ethylene oxide) (PEO)-silane amphiphiles that demonstrated a higher capacity to restructure to the surface-water interface versus conventional non-amphiphilic PEO-silanes. The PEO-silane amphiphiles were prepared with a single siloxane tether length but variable PEO segment lengths: α-(EtO)3Si(CH2)2-oligodimethylsiloxane13-block-poly(ethylene oxide)n-OCH3 (n = 3, 8, and 16). Conventional PEO-silane analogu...

  5. 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...

  6. 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).

  7. 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...

  8. Short stature

    Science.gov (United States)

    ... St Geme JW III, Schor NF, eds. Nelson Textbook of Pediatrics . 20th ed. Philadelphia, PA: Elsevier; 2016:chap 15. Sisley S, Trujillo MV, Khoury J, Backeljauw P. Low incidence of pathology detection and high cost of screening in the evaluation of symptomatic short ...

  9. Short stature

    Science.gov (United States)

    ... TREATMENT Your child's short stature may affect her self-esteem. Check in with your child about relationships with ... GH treatment limited to the prepubertal period in young children ... not increase adult height. Eur J Endocrinol . 2010;162(4):653- ...

  10. Peptides as catalysts in the RNA world

    DEFF Research Database (Denmark)

    Wieczorek, Rafal; Dörr, Mark; Luisi, Pier Luigi;

    the RNA world concept. Contrary to RNA building blocks, amino acids form quite easily in simulated prebiotic reactions. Also, many prebiotic scenarios for condensation of amino acids into peptides have been proposed and successfully demonstrated experimentally (Rode 1999). We also have growing body of...... experimental evidence showing various catalytic activities associated with short chain peptides, some of them as small as dipeptides. One such peptide, composed of only two amino acid residues; serine and histidine, was reported to exhibit broad hydrolytic activities. The dipeptide SerHis can catalyze the...... hydrolysis of esters, proteins and nucleic acids (Li et al. 2000). The direction of the catalysis either toward hydrolysis or condensation is determined by thermodynamic constraints. In an aqueous medium (a general requirement for prebiotically compatible reactions), hydrolysis is thermodynamically favored...

  11. 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.

  12. Organization of T-shaped facial amphiphiles at the air/water interface studied by infrared reflection absorption spectroscopy.

    Science.gov (United States)

    Schwieger, Christian; Chen, Bin; Tschierske, Carsten; Kressler, Jörg; Blume, Alfred

    2012-10-11

    We studied the behavior of monolayers at the air/water interface of T-shaped facial amphiphiles which show liquid-crystalline mesophases in the bulk. The compounds are composed of a rigid p-terphenyl core (TP) with two terminal hydrophobic ether linked alkyl chains of equal length and one facial hydrophilic tri(ethylene oxide) chain with a carboxylic acid end group. Due to their amphiphilic nature they form stable Langmuir films at the air/water interface. Depending on the alkyl chain length they show markedly different compression isotherms. We used infrared reflection absorption spectroscopy (IRRAS) to study the changes in molecular organization of the TP films upon compression. We could retrieve information on layer thickness, alkyl chain crystallization, and the orientation of the TP cores within the films. Films of TPs with long (16 carbon atoms: TP 16/3) and short (10 carbon atoms: TP 10/3) alkyl chains were compared. Compression of TP 16/3 leads to crystallization of the terminal alkyl chains, whereas the alkyl chains of TP 10/3 stay fluid over the complete compression range. TP 10/3 shows an extended plateau in the compression isotherm which is due to a layering transition. The mechanism of this layering transition is discussed. Special attention was paid to the question of whether a so-called roll-over collapse occurs during compression. From the beginning to the end of the plateau, the layer thickness is increased from 15 to 38 Å and the orientation of the TP cores changes from parallel to the water surface to isotropic. We conclude that the plateau in the compression isotherm reflects the transition of a TP monolayer to a TP multilayer. The monolayer consists of a sublayer of well-organized TP cores underneath a sublayer of fluid alkyl chains whereas the multilayer consists of a well oriented bottom layer and a disordered top layer. Our findings do not support the model of a roll-over collapse. This study demonstrates how the IRRA band intensity of OH

  13. 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.

  14. 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 produced by the body and insulin injected ...

  15. 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.

  16. 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 a...

  17. PNA Peptide chimerae

    DEFF Research Database (Denmark)

    Koch, T.; Næsby, M.; Wittung, P.; Jørgensen, M.; Larsson, C.; Buchardt, O.; Stanly, C.J.; Norden, B.; Nielsen, P.E.; Ørum, H.

    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.......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....

  18. Long Circulating Micelles based on Helix Bundle-Forming Peptide-Polymer Conjugates

    Science.gov (United States)

    Shu, Jessica; Dong, He; Dube, Nikhil; Seo, Jai Woong; Ma, Yu Fei; Ferrara, Katherine; Xu, Ting

    2012-02-01

    Stable, multi-functional organic nanoparticles that combine long in vivo circulation, the ability to cross vessel walls to reach tumor tissues and controlled disassembly for eventual clearance will have a significant impact in nanomedicine. Although current self-assemblies of amphiphiles provide a versatile platform to generate modular organic nanoparticles, it remains a significant challenge to simultaneously control nanoparticle size in the range of 10-30 nm, enhance particle stability and tailor disassembly within suitable timescales. We have advanced this goal by designing a new family of amphiphiles based on coiled-coil 3-helix bundle forming peptide-polymer conjugates. By attaching a polymer chain to the middle of a helical peptide, the protein tertiary structures are used to position entropic forces of compressed polymer chains comprising the headgroups so as to effectively slow down the subunit desorption rate and enhance the in vivo stability. The resultant monodispersed nanoparticles are composed of subunits, polymer chain with a common protein structure, i.e. coiled-coil helix bundle, and a lipid core, self-assembled nanoparticles have been engineered with tunable stability and disassembly.

  19. 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.

  20. The efficiency of peptide immunotherapy for respiratory allergy.

    Science.gov (United States)

    Incorvaia, Cristoforo; Montagni, Marcello; Ridolo, Erminia

    2016-06-01

    Allergen immunotherapy (AIT) was introduced more than a century ago and is yet the only disease-modifying treatment for allergy. AIT is currently conducted with whole allergen extracts and several studies clearly support its efficacy in the treatment of respiratory allergies, however the need for a long treatment - that affects costs and patients compliance - and possible IgE-mediated adverse events are still unresolved issues. Peptide immunotherapy is based on the use of short synthetic peptides which represent major T-cell epitopes of the allergen with markedly reduced ability to cross-link IgE and activate mast cells and basophils. Data from clinical trials confirmed the efficacy and tolerability of peptide immunotherapy in patients with cat allergy, with a sustained clinical effect after a short course treatment. Peptide therapy is a promising safe and effective new specific treatment for allergy to be developed for the most important allergens causing rhinitis or asthma. PMID:26901667

  1. 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.

  2. 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.

  3. 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...

  4. 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

  5. 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.

  6. 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.

  7. 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....

  8. 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...

  9. Identifying reactive peptides from phage-displayed libraries

    Science.gov (United States)

    Eldridge, Glenn M.; Weiss, Gregory A.

    2015-01-01

    Summary Phage display enables the synthesis, selection and screening of large, polypeptide libraries (>1 × 1010). Selections from such libraries can identify binding partners to essentially any desired target (1, 2). Peptide with affinity or reactivity to small molecule probes are attractive for numerous uses including the targeted, site-specific labeling of proteins. Here, we describe selection and screening protocols for the identification of short peptides that can selectively bind to and/or react with small molecules. PMID:25616334

  10. Supramolecular Polymers Formed by ABC Miktoarm Star Peptides

    OpenAIRE

    Lin, Yi-an; Ou, Yu-Chuan; Cheetham, Andrew G.; Cui, Honggang

    2013-01-01

    We report here the design and synthesis of an ABC miktoarm star peptide connecting through a lysine junction a short peptide sequence and two hydrophobic but immiscible blocks (a hydrocarbon and a fluorocarbon). The designed molecule can self-assemble into one-dimensional nanostructures with a great diversity of kinetically evolving morphologies in aqueous solution, while molecules that contain only one of the two hydrophobic blocks form structurally similar filaments. We believe the rich ass...

  11. 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...

  12. 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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-05-01

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

  14. Site-specific C-functionalization of free-(NH) peptides and glycine derivatives via direct C–H bond functionalization

    OpenAIRE

    Zhao, Liang; Baslé, Oliver; Li, Chao-Jun

    2009-01-01

    A copper-catalyzed α-functionalization of glycine derivatives and short peptides with nucleophiles is described. The present method provides ways to introduce functionalities such as aryl, vinyl, alkynyl, or indolyl specifically to the terminal glycine moieties of small peptides, which are normally difficult in peptide modifications. Furthermore, on functionalization, the configurations of other stereocenters in the peptides could be maintained. Because the functionalized peptides could easil...

  15. Descriptors for antimicrobial peptides

    DEFF Research Database (Denmark)

    Jenssen, Håvard

    2011-01-01

    Introduction: A frightening increase in the number of isolated multidrug resistant bacterial strains linked to the decline in novel antimicrobial drugs entering the market is a great cause for concern. Cationic antimicrobial peptides (AMPs) have lately been introduced as a potential new class of...... antimicrobial drugs, and computational methods utilizing molecular descriptors can significantly accelerate the development of new peptide drug candidates. Areas covered: This paper gives a broad overview of peptide and amino-acid scale descriptors available for AMP modeling and highlights which of these are...

  16. 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.

  17. 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

  18. 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

  19. 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...... 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 for the...

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

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Qiu Liyan [College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058 (China); Zhang Jianxiang [College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058 (China); Yan Meiqiu [College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058 (China); Jin Yi [College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058 (China); Zhu Kangjie [Institute of Polymer Science, Zhejiang University, Hangzhou 310027 (China)

    2007-11-28

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

  2. 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.

  3. Imaging Pseudomonas aeruginosa Biofilm Extracellular Polymer Scaffolds with Amphiphilic Carbon Dots.

    Science.gov (United States)

    Ritenberg, Margarita; Nandi, Sukhendu; Kolusheva, Sofiya; Dandela, Rambabu; Meijler, Michael M; Jelinek, Raz

    2016-05-20

    Biofilm formation is a critical facet of pathogenesis and resilience of human, animal, and plant bacteria. Extracellular polymeric substances (EPS) constitute the physical scaffolding for bacterial biofilms and thus play central roles in their development and virulence. We show that newly synthesized amphiphilic fluorescent carbon dots (C-dots) readily bind to the EPS scaffold of Pseudomonas aeruginosa, a major biofilm-forming pathogen, resulting in unprecedented microscopic visualization of the EPS structural features. Fluorescence microscopy analysis utilizing the C-dots reveals that the P. aeruginosa EPS matrix exhibits a remarkable dendritic morphology. The experiments further illuminate the growth kinetics of the EPS and the effect of external factors such as temperature. We also show that the amphiphilic C-dot platform enabled screening of substances disrupting biofilm development, specifically quorum sensing inhibitors. PMID:26882175

  4. 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.

  5. 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.

  6. 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

  7. A V-shaped polyaromatic amphiphile: solubilization of various nanocarbons in water and enhanced photostability.

    Science.gov (United States)

    Kondo, Kei; Akita, Munetaka; Nakagawa, Takafumi; Matsuo, Yutaka; Yoshizawa, Michito

    2015-09-01

    Nanocarbons are synthetic carbon-rich compounds with polyaromatic frameworks that have lately attracted attention as emerging functional materials. However, their extreme hydrophobicity and aggregation peculiarity, besides their shape and size diversities, precluded their study in solution, especially in "green" water. More convenient and general solubilizing methods of nanocarbon frameworks are required by using non-covalent supramolecular interactions. Here we report a protocol for solubilizing a wide range of nanocarbons, that is, fullerenes (C60 , C70 , C84 , and C120 ), polyarenes (tetracene, pentacene, perylene, coronene, and hexabenzocoronene), and carbon nanotubes (single-walled and multi-walled CNTs), in water through manual grinding with V-shaped polyaromatic amphiphiles. The obtained aqueous nanocomposites are composed of nanocarbons encircled by the polyaromatic frameworks of the amphiphiles through multiple aromatic-aromatic interactions. Notably, the encapsulated photosensitive nanocarbons, such as tetracene, pentacene, and fullerene dimer, exhibit unusual stability toward UV/Vis light. PMID:26224472

  8. 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.

  9. Novel Xylene-Linked Maltoside Amphiphiles (XMAs) for Membrane Protein Stabilisation

    DEFF Research Database (Denmark)

    Cho, Kyung Ho; Du, Yang; Scull, Nicola J; Hariharan, Parameswaran; Gotfryd, Kamil; Loland, Claus J; Guan, Lan; Byrne, Bernadette; Kobilka, Brian K; Chae, Pil Seok

    2015-01-01

    . Conventional detergents are commonly used for membrane protein manipulation, but membrane proteins surrounded by these agents often undergo denaturation and aggregation. In this study, a novel class of maltoside-bearing amphiphiles, with a xylene linker in the central region, designated xylene-linked maltoside......Membrane proteins are key functional players in biological systems. These biomacromolecules contain both hydrophilic and hydrophobic regions and thus amphipathic molecules are necessary to extract membrane proteins from their native lipid environments and stabilise them in aqueous solutions...... amphiphiles (XMAs) was developed. When these novel agents were evaluated with a number of membrane proteins, it was found that XMA-4 and XMA-5 have particularly favourable efficacy with respect to membrane protein stabilisation, indicating that these agents hold significant potential for membrane protein...

  10. 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.)

  11. 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.

  12. Novel Amphiphilic copolymers and design of smart nanoparticule for triggered drug delivery systems

    OpenAIRE

    Cajot, Sébastien; Jérôme, Christine

    2009-01-01

    Over the last decade, polymer micelles attracted an increasing interest in drug pharmaceutical research because they could be used as efficient drug delivery systems. Micelles of amphiphilic block copolymers are supramolecular core-shell type assemblies of tens of nanometers in diameter. In principle, the micelles core is usually constructed with biodegradable hydrophobic polymers such as aliphatic polyesters, e.g. poly(epsilon-caprolactone) (PCL), which serves as a reservoir for the inc...

  13. 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...

  14. 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...

  15. 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...

  16. 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 ...

  17. 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...

  18. 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

  19. 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 ...

  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. Non-ionic amphiphilic block copolymers by RAFT-polymerization and their self-organization

    OpenAIRE

    Garnier, Sébastien; Laschewsky, André

    2006-01-01

    Water-soluble, amphiphilic diblock copolymers were synthesized by reversible addition fragmentation chain transfer polymerization. They consist of poly(butyl acrylate) as hydrophobic block with a low glass transition temperature and three different nonionic water-soluble blocks, namely, the classical hydrophilic block poly(dimethylacrylamide), the strongly hydrophilic poly(acryloyloxyethyl methylsulfoxide), and the thermally sensitive poly(N-acryloylpyrrolidine). Aqueous micellar solutions of...

  2. 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. PMID:15927586

  3. 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...

  4. 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-...

  5. 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.

  6. 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

  7. The effect of amphiphilic siloxane oligomers on fibroblast and keratinocyte proliferation and apoptosis.

    Science.gov (United States)

    Lynam, Emily C; Xie, Yan; Loli, Bree; Dargaville, Tim R; Leavesley, David I; George, Graeme A; Upton, Zee

    2010-11-01

    The formation of hypertrophic scars (HSF) is a frequent medical outcome of wound repair and often requires further therapy with treatments such as silicone gel sheets (SGS) or apoptosis-inducing agents, including bleomycin. Although widely used, knowledge regarding SGS and their mode of action is limited. Preliminary research has shown that small amounts of amphiphilic silicone present in SGS have the ability to move into skin during treatment. We demonstrate herein that a commercially available analogue of these amphiphilic siloxane species, the rake copolymer GP226, decreases collagen synthesis on exposure to cultures of fibroblasts derived from HSF. By size exclusion chromatography, GP226 was found to be a mixture of siloxane species, containing five fractions of different molecular weight. By studies of collagen production, cell viability and proliferation, it was revealed that a low molecular weight fraction (fraction IV) was the most active, reducing the number of viable cells present after treatment and thereby reducing collagen production as a result. On exposure of fraction IV to human keratinocytes, viability and proliferation were also significantly affected. HSF undergoing apoptosis after application of fraction IV were also detected via real-time microscopy and by using the TUNEL assay. Taken together, these data suggests that these amphiphilic siloxanes could be potential non-invasive substitutes to apoptotic-inducing chemical agents that are currently used as scar treatments. PMID:20725963

  8. 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

  9. 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.

  10. Nanostructure protein repellant amphiphilic copolymer coatings with optimized surface energy by Inductively Excited Low Pressure Plasma.

    Science.gov (United States)

    Bhatt, Sudhir; Pulpytel, Jérome; Ceccone, Giacomo; Lisboa, Patricia; Rossi, François; Kumar, Virendra; Arefi-Khonsari, Farzaneh

    2011-12-01

    Statistically designed amphiphilic copolymer coatings were deposited onto Thermanox, Si wafer, and quartz crystal microbalance (QCM) substrates via Plasma Enhanced Chemical Vapor Deposition of 1H,1H,2H,2H-perfluorodecyl acrylate and diethylene glycol vinyl ether in an Inductively Excited Low Pressure Plasma reactor. Plasma deposited amphiphilic coatings were characterized by Field Emission Scanning Electron Microscopy, X-ray Photoelectron Spectroscopy, Atomic Force Microscopy, and Water Contact Angle techniques. The surface energy of the coatings can be adjusted between 12 and 70 mJ/m(2). The roughness of the coatings can be tailored depending on the plasma mode used. A very smooth coating was deposited with a CW (continuous wave) power, whereas a rougher surface with R(a) in the range of 2 to 12 nm was deposited with the PW (pulsed wave) mode. The nanometer scale roughness of amphiphilic PFDA-co-DEGVE coatings was found to be in the range of the size of the two proteins namely BSA and lysozyme used to examine for the antifouling properties of the surfaces. The results show that the statistically designed surfaces, presenting a surface energy around 25 mJ/m(2), present no adhesion with respect to both proteins measured by QCM. PMID:22029599

  11. 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.

  12. 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

  13. 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.

  14. 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....

  15. 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

  16. 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.

  17. Tumor penetrating peptides

    Directory of Open Access Journals (Sweden)

    ErkkiRuoslahti

    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

  18. 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.

  19. 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

  20. 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

  1. Critical Assessment of Current Force Fields. Short Peptide Test Case

    Czech Academy of Sciences Publication Activity Database

    Vymětal, Jiří; Vondrášek, Jiří

    2013-01-01

    Roč. 9, č. 1 (2013), s. 441-451. ISSN 1549-9618 R&D Projects: GA MŠk(CZ) LH11020 Grant ostatní: GA MŠk(CZ) LM2010005 Institutional support: RVO:61388963 Keywords : Helix-coil transition * protein-folding simulations * amino-acids * side- chain * alanine dipeptide Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 5.310, year: 2013

  2. Improved stability and selectivity of lytic peptides through self-assembly

    International Nuclear Information System (INIS)

    Widespread clinical applications of peptide drugs have been hindered by their low stability and selectivity. Peptides can be easily digested by various enzymes in the blood and thus show a short life-span. Meanwhile, peptide drugs can cause severe normal tissue damage due to their low selectivity. Therefore, for effective therapy, a high dosage of peptide is required which is usually in excess of the clinically and economically acceptable level. In this study, we have tried to design new lytic peptides which can self-assemble into peptide fibrils with defined nanostructures as observed under atomic force microscopy. Lytic peptides in self-assembled peptide fibrils will lose their cell lysis activity but become resistant to enzyme degradation. Such lytic peptide self-assembly has proven to be a reversible process which is controlled by surrounded environments. A concentration controlled sustained release of free and active lytic peptide from self-assembled peptide fibrils has been achieved. Self-assembled lytic peptides with enzyme resistance, sustained release, and prodrug feature may have great clinical application potentials

  3. 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.

  4. 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.

  5. 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. PMID:26723588

  6. 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.

  7. Novel approaches to short stature therapy.

    Science.gov (United States)

    Wit, Jan M; Oostdijk, Wilma

    2015-06-01

    Besides growth hormone, several pharmaceutical products have been investigated for efficacy and safety in increasing short term growth or adult height. Short-term treatment with testosterone esters in boys with constitutional delay of growth and puberty is efficacious in generating secondary sex characteristics and growth acceleration. The addition of oxandrolone to growth hormone (GH) in Turner syndrome has an additive effect on adult height gain. Treatment with GnRH analogs is the established treatment of central precocious puberty, and its addition to GH therapy appears effective in increasing adult height in GH deficient children, and possibly short children born SGA or with SHOX deficiency, who are still short at pubertal onset. Aromatase inhibitors appear effective in several rare disorders, but their value in increasing adult height in early pubertal boys with GH deficiency or idiopathic short stature is uncertain. A trial with a C-natriuretic peptide analog offers hope for children with achondroplasia. PMID:26051296

  8. 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.

  9. 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

  10. 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

  11. 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.

  12. 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

  13. 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.

  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. 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

  16. Peptide catalysed prebiotic polymerization of RNA

    DEFF Research Database (Denmark)

    Wieczorek, Rafal; Luisi, Pier Luigi; Monnard, Pierre-Alain

    A short peptide composed of only two amino acid residues, serine and histidine, is here reported to enable oligomerization of RNA monomers. SerHis dipeptide was previously reported to catalyse formation of peptide bonds (Gorlero et al. 2009) as well as possessing broad hydrolytic activities...... oligomers from imidazole derivatives of mononucleotides. The thermodynamic shift towards condensation was achieved using water/ice eutectic phase environment (Monnard and Ziock 2008). To obtain such an environment, a reaction solution is cooled below its freezing point, but above the eutectic point. Under....... (2000) Dipeptide seryl-histidine and related oligopeptides cleave DNA, protein, and a carboxyl ester. Bioorg. Med. Chem. 8(12): 2675-80. Monnard PA, Ziock H. (2008) Eutectic phase in water-ice: a self-assembled environment conducive to metal-catalyzed non-enzymatic RNA polymerization. Chem Biodivers. 5...

  17. 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

  18. Construction of amphiphilic segments on polypropylene nonwoven surface and its application in removal of endocrine disrupting compounds (EDCs) from aqueous solution

    International Nuclear Information System (INIS)

    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

  19. 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.

  20. Therapeutic HIV Peptide Vaccine

    DEFF Research Database (Denmark)

    Fomsgaard, Anders

    2015-01-01

    Therapeutic vaccines aim to control chronic HIV infection and eliminate the need for lifelong antiretroviral therapy (ART). Therapeutic HIV vaccine is being pursued as part of a functional cure for HIV/AIDS. We have outlined a basic protocol for inducing new T cell immunity during chronic HIV-1...... infection directed to subdominant conserved HIV-1 epitopes restricted to frequent HLA supertypes. The rationale for selecting HIV peptides and adjuvants are provided. Peptide subunit vaccines are regarded as safe due to the simplicity, quality, purity, and low toxicity. The caveat is reduced immunogenicity...

  1. 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

  2. Biosynthesis of cardiac natriuretic peptides

    DEFF Research Database (Denmark)

    Goetze, Jens Peter

    2010-01-01

    Cardiac-derived peptide hormones were identified more than 25 years ago. An astonishing amount of clinical studies have established cardiac natriuretic peptides and their molecular precursors as useful markers of heart disease. In contrast to the clinical applications, the biogenesis of cardiac p...... competent endocrine cells. The structurally related atrial natriuretic peptide will be mentioned where appropriate, whereas C-type natriuretic peptide will not be considered as a cardiac peptide of relevance in mammalian physiology....... characterized. An ongoing characterization of the molecular heterogeneity will help appreciate the biosynthetic capacity of the endocrine heart and could introduce new diagnostic possibilities. Notably, different biosynthetic products may not be equal markers of the same pathophysiological processes. An...... inefficient post-translational prohormone maturation will also affect the biology of the cardiac natriuretic peptide system. This review aims at summarizing the myocardial synthesis of natriuretic peptides focusing on B-type natriuretic peptide, where new data has disclosed cardiac myocytes as highly...

  3. Biosynthesis of cardiac natriuretic peptides

    DEFF Research Database (Denmark)

    Goetze, Jens Peter

    2010-01-01

    Cardiac-derived peptide hormones were identified more than 25 years ago. An astonishing amount of clinical studies have established cardiac natriuretic peptides and their molecular precursors as useful markers of heart disease. In contrast to the clinical applications, the biogenesis of cardiac...... inefficient post-translational prohormone maturation will also affect the biology of the cardiac natriuretic peptide system. This review aims at summarizing the myocardial synthesis of natriuretic peptides focusing on B-type natriuretic peptide, where new data has disclosed cardiac myocytes as highly...... competent endocrine cells. The structurally related atrial natriuretic peptide will be mentioned where appropriate, whereas C-type natriuretic peptide will not be considered as a cardiac peptide of relevance in mammalian physiology....

  4. 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....

  5. 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. PMID:26651013

  6. Effects of amphiphilic agent on thermal conductivity of boron nitride/poly(vinyl butyral) composites

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Hong Jun [Department of Materials Engineering, Kyonggi University, Suwon (Korea, Republic of); Cha, Sang-Ho [Department of Chemical Engineering, Kyonggi University, Suwon (Korea, Republic of); Lee, Woo Sung [Electronic Materials and Device Research Center, Korea Electronics Technology Institute, Seongnam (Korea, Republic of); Kim, Eung Soo, E-mail: eskim@kyonggi.ac.kr [Department of Materials Engineering, Kyonggi University, Suwon (Korea, Republic of)

    2014-09-10

    Highlights: • The platelet BN particles were oriented in poly(vinyl butyral) (PVB) matrix by tape-casting process. • The degree of BN orientation was estimated from XRD patterns of BN/PVB composites. • Surface treatment of BN with amphiphilic agent was confirmed by FT-IR and elemental analysis. • The BN/PVB composites with in-plane oriented 8-μm-sized BN particles showed a higher thermal conductivity than the other composites. - Abstract: Dependence of thermal conductivity of boron nitride (BN)/poly(vinyl butyral) (PVB) composites on the orientation and particle size of BN with an amphiphilic agent was investigated. The platelet BN particles were oriented in the polymer matrix by physical processes such as tape-casting process. A comparison of the thermal conductivity of the specimens with that of pristine BN showed that the BN/PVB composite treated with amphiphilic agents such as C{sub 14}H{sub 6}O{sub 8} and C{sub 27}H{sub 27}N{sub 3}O{sub 2} showed a higher thermal conductivity than the PVB composite with pristine BN. It was also found that the thermal conductivity of the C{sub 14}H{sub 6}O{sub 8}-treated BN/PVB composite was higher than that of the C{sub 27}H{sub 27}N{sub 3}O{sub 2}-treated composite due to the good dispersion and interfacial adhesion with C{sub 14}H{sub 6}O{sub 8}. Also, the thermal conductivity of the composite with an in-plane orientation of 8-μm-sized BN was higher than that of the composites with different particles sizes because of the improvement in the high degree of orientation.

  7. 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.

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

    DEFF Research Database (Denmark)

    Eenschooten, Corinne; Vaccaro, Andrea; Delie, Florence;

    2012-01-01

    The purpose of the present study was to investigate the physicochemical properties in aqueous media of amphiphilic hyaluronic acid (HA) derivatives obtained by reaction of HA’s hydroxyl groups with octenyl succinic anhydride (OSA). The self-associative properties of the resulting octenyl succinic...... anhydridemodified hyaluronic acid (OSA-HA) derivatives were studied by fluorescence spectroscopy using Nile Red as fluorophore. The morphology, size and surface charge of the OSA-HA assemblies were determined by transmission electron microscopy, dynamic light scattering and by measuring their electrophoretic...

  9. Plasmonic Vesicles of Amphiphilic Nanocrystals: Optically Active Multifunctional Platform for Cancer Diagnosis and Therapy.

    Science.gov (United States)

    Song, Jibin; Huang, Peng; Duan, Hongwei; Chen, Xiaoyuan

    2015-09-15

    Vesicular structures with compartmentalized, water-filled cavities, such as liposomes of natural and synthetic amphiphiles, have tremendous potential applications in nanomedicine. When block copolymers self-assemble, the result is polymersomes with tailored structural properties and built-in releasing mechanisms, controlled by stimuli-responsive polymer building blocks. More recently, chemists are becoming interested in multifunctional hybrid vesicles containing inorganic nanocrystals with unique optical, electronic, and magnetic properties. In this Account, we review our recent progress in assembling amphiphilic plasmonic nanostructures to create a new class of multifunctional hybrid vesicles and applying them towards cancer diagnosis and therapy. Localized surface plasmon resonance (LSPR) gives plasmonic nanomaterials a unique set of optical properties that are potentially useful for both biosensing and nanomedicine. For instance, the strong light scattering at their LSPR wavelength opens up the applications of plasmonic nanostructures in single particle plasmonic imaging. Their superior photothermal conversion properties, on the other hand, make them excellent transducers for photothermal ablation and contrast agents for photoacoustic imaging. Of particular note for ultrasensitive detection is that the confined electromagnetic field resulting from excitation of LSPR can give rise to highly efficient surface enhanced Raman scattering (SERS) for molecules in close proximity. We have explored several ways to combine well-defined plasmonic nanocrystals with amphiphilic polymer brushes of diverse chemical functionalities. In multiple systems, we have shown that the polymer grafts impart amphiphilicity-driven self-assembly to the hybrid nanoparticles. This has allowed us to synthesize well-defined vesicles in which we have embedded plasmonic nanocrystals in the shell of collapsed hydrophobic polymers. The hydrophilic brushes extend into external and interior aqueous

  10. Two-dimensional crystallography of amphiphilic molecules at the air-water interface

    DEFF Research Database (Denmark)

    Jacquemain, D.; Grayer Wolf, S.; Leveiller, F.; Deutsch, M.; Kjær, K.; Als-Nielsen, J.; Lahav, M.; Leiserowitz, L.

    1992-01-01

    review recent results obtained from them for Langmuir films. The methods have been successfully applied in the elucidation of the structure of crystalline aggregates of amphiphilic molecules such as alcohols, carboxylic acids and their salts, alpha-amino acids, and phospholipids at the water surface. In...... solute species. Examples are given where singly or doubly charged ions bound to the two-dimensional (2D) crystal form either an ordered or diffuse counterionic layer. Finally, the surface diffraction methods provide data on transfer of structural information from 2D clusters to 3D single crystals, which...... had been successfully accomplished by epitaxial-like crystallization both in organic and inorganic crystals....

  11. Control of structure and growth of polymorphic crystalline thin films of amphiphilic molecules on liquid surfaces

    DEFF Research Database (Denmark)

    Weinbach, S.P.; Kjær, K.; Bouwman, W.G.;

    1994-01-01

    The spontaneous formation and coexistence of crystalline polymorphic trilayer domains in amphiphilic films at air-liquid interfaces is demonstrated by grazing incidence synchrotron x-ray diffraction. These polymorphic crystallites may serve as models for the early stages of crystal nucleation and...... growth, helping to elucidate the manner in which additives influence the progress of crystal nucleation, growth, and polymorphism and suggesting ways of selectively generating and controlling multilayers on liquid surfaces. Auxiliary molecules have been designed to selectively inhibit development of the...

  12. Self-assembling Behavior of Amphiphilic Copolymer Containing Cross-linked Hydrophilic Block in Ethanol

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The self-assembly behavior of the amphiphilic block copolymer poly( methyl methacrylate)-block-poly( lead dimethacrylate) (PMMA-b-PLDMA) with cross-linked hydrophilic block (PLDMA) in ethanol was investigated. The results show that the size and morphology of the resulting micelle or micellar aggregates are ascribed to the content of ethanol and the nature of the solvent mixture. PbS nanoparticles were formed in the micelle by in situ reaction with H2S gas. The morphology and size of the self-assembly objects were investigated using scanning electron microscopy (SEM) and transmission electron microscopy (TEM).

  13. A spectroscopic method to estimate the binding potency of amphiphile assemblies

    Czech Academy of Sciences Publication Activity Database

    Gauger, D. R.; Andrushchenko, Valery; Bouř, Petr; Pohle, W.

    2010-01-01

    Roč. 398, č. 2 (2010), s. 1109-1123. ISSN 1618-2642 R&D Projects: GA ČR GA203/06/0420; GA ČR GA202/07/0732; GA ČR GAP208/10/0559; GA AV ČR IAA400550702; GA AV ČR IAA400550701 Institutional research plan: CEZ:AV0Z40550506 Keywords : miccels * amphiphile assemblies * molecular dynamics * infrared spectroscopy Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.841, year: 2010

  14. Theoretical estimation of the critical packing parameter of amphiphilic self-assembled aggregates

    Energy Technology Data Exchange (ETDEWEB)

    Khalil, Rabah A., E-mail: rakhalil64@yahoo.com; Zarari, Al-hakam A.

    2014-11-01

    Graphical abstract: - Highlights: • Critical packing parameter (p) is an important property for self-assembled aggregate. • Up to date, the estimation of p is regarded as hypothetical rather than empirical. • The results announce the possibility of predicting p theoretically using DFT method. • Possibility of employing the evaluation of p through computational chemistry software. • Valuable thermodynamic information about the self-assembly may be obtained from determined p. - Abstract: The estimating of critical packing parameter (p) of amphiphilic compounds is considered as a hypothetical rather than an empirical. Consequently, an attempt has been made for determining such a dimensionless parameter for homologous series of sodium p-n-alkyl benzoates (n = 0–8) hydrotropes using quantum mechanical calculations that depend on density functional theory (DFT). The calculations were based on the following well-defined model, p = v/a{sub 0}l{sub c}, where v is the volume of the hydrotrope tail, a{sub 0} is the effective head group area and l{sub c} is the length of the extended hydrotrope tail. It was found that the magnitude of both v and l{sub c} parameters can be estimated directly from quantum mechanical calculations. While the investigations found that the a{sub 0} parameter is parallel to the Connolly solvent accessible surface area (C{sub sa}) which could also be determined through theoretical computations. The obtained results were in good agreement with published data using small angle neutron scattering (SANS) technique. Hence, the theoretical model for predicting p of amphiphilic at critical micelle- or aggregation-concentration (cmc or cac) is p = v/C{sub sa}l{sub c}. An apparent success was observed through applying this simple model to some randomly selected surfactants. It has been concluded that the theoretical calculations that based on quantum mechanical (DFT) method can be considered as a powerful tool for estimating the critical packing

  15. Macroscopic alignment of graphene stacks by Langmuir-Blodgett deposition of amphiphilic hexabenzocoronenes

    DEFF Research Database (Denmark)

    Laursen, B.W.; Nørgaard, K.; Reitzel, N.;

    2004-01-01

    e present structural studies of Langmuir V and Langmuir-Blodgett (LB) films of new amphiphilic hexa-peri-hexabenzocoronene (HBC) discotics, carrying five branched alkyl side chains and one polar group. The polar group is either a carboxylic acid moiety or an electron acceptor moiety (anthraquinone...... tilted relative to the water surface. The intercolumnar distance is 20 A. The HBCs are confined to a layer lying on top of the layer of polar groups that are in contact with the water subphase. Efficient transfer of the monolayer of the anthraquinone-substituted HBC derivative to hydrophobic quartz...

  16. Small angle neutron scattering study of the micelle structure of amphiphilic block copolymers

    International Nuclear Information System (INIS)

    The amphiphilic block copolymers of vinyl ether were prepared by living cationic polymerization. The partially deuterated copolymers for SANS experiments were especially synthesized by introducing deuterated phenyl units in the hydrophobic chain. SANS measurements were performed for aqueous solutions of these copolymers by changing H2O/D2O ratios. The SANS profiles indicate that the micelles in the present system exhibit a core-shell structure and that the size and shape of micelles are largely dependent on the length of hydrophobic chain. The micelle of shorter hydrophobic chain was found to be nearly spherical, whereas the micelle of longer hydrophobic chain was confirmed to have an ellipsoidal shape

  17. Synthesis, Characterization, Critical Micelle Concentration and Biological Activity of two-Headed Amphiphiles

    OpenAIRE

    Actis, Marcelo

    2008-01-01

    In this project, we synthesized a new homologous series of five long-chain, two-headed amphiphiles [2CAm13, 2CAm15, 2CAm17, 2CAm19, 2CAm21; CH3(CH2)n-1CONHC(CH3)(CH2CH2COOH)2, n = 13, 15, 17, 19, 21]. The synthesis of the 2CAmn series was accomplished in four steps. The first step involves a reaction of nitroethane and two equivalents of tert-butyl acrylate to create the nitrodiester synthon [O2NC(CH3)(CH2CH2COOtBu)2] by successive Michael additions. The second step in the synthesi...

  18. Amphiphilic copolymer coated upconversion nanoparticles for near-infrared light-triggered dual anticancer treatment

    Science.gov (United States)

    Yang, Shun; Li, Najun; Liu, Zhuang; Sha, Wenwei; Chen, Dongyun; Xu, Qingfeng; Lu, Jianmei

    2014-11-01

    The light-triggered controlled release of anticancer drugs accompanied with NIR-responsive photodynamic therapy was prepared via a self-assembly process. Firstly, Mn2+-doped upconversion nanoparticles (UCNPs) were coated with a mesoporous silica shell and modified with photosensitizer (Chlorin e6) and long alkyl chains. And then the NIR light-responsive amphiphilic copolymer containing 9,10-dialkoxyanthracene groups was synthesized and then coated as the outermost layer. Upon irradiation with a 980 nm laser, the CCUCNPs@PM would absorb and then convert the NIR light to higher-energy visible red light (660 nm) via the UCNPs-based core, which could excite Chlorin e6 (Ce-6) to produce singlet oxygen (1O2). Then the 1O2-sensitive dialkoxyanthracene group in the amphiphilic copolymer would be degraded and detach from the surface of the CCUCNPs@PM, followed by the controlled release of the pre-loaded drugs and the photodynamic therapy for cancer cells caused by the excess 1O2. In vitro and in vivo experiments also demonstrated that the drug-loaded CCUCNPs@PM possessed better therapeutic efficacy compared with vacant ones. Therefore, the NIR light-controlled chemotherapy and photodynamic therapy could be realized simultaneously by CCUCNPs@PM.The light-triggered controlled release of anticancer drugs accompanied with NIR-responsive photodynamic therapy was prepared via a self-assembly process. Firstly, Mn2+-doped upconversion nanoparticles (UCNPs) were coated with a mesoporous silica shell and modified with photosensitizer (Chlorin e6) and long alkyl chains. And then the NIR light-responsive amphiphilic copolymer containing 9,10-dialkoxyanthracene groups was synthesized and then coated as the outermost layer. Upon irradiation with a 980 nm laser, the CCUCNPs@PM would absorb and then convert the NIR light to higher-energy visible red light (660 nm) via the UCNPs-based core, which could excite Chlorin e6 (Ce-6) to produce singlet oxygen (1O2). Then the 1O2-sensitive

  19. Lattice-Gas Simulations of Ternary Amphiphilic Fluid Flow in Porous Media

    CERN Document Server

    Coveney, P V; Wilson, J L; Fowler, P W; Al-Mushadani, O; Boghosian, B M

    1998-01-01

    We develop our existing two-dimensional lattice-gas model to simulate the flow of single-phase, binary-immiscible and ternary-amphiphilic fluids. This involves the inclusion of fixed obstacles on the lattice, together with the inclusion of ``no-slip'' boundary conditions. Here we report on preliminary applications of this model to the flow of such fluids within model porous media. We also construct fluid invasion boundary conditions, and the effects of invading aqueous solutions of surfactant on oil-saturated rock during imbibition and drainage are described.

  20. Water-repellent textile via decorating fibers with amphiphilic Janus particles.

    Science.gov (United States)

    Synytska, Alla; Khanum, Rina; Ionov, Leonid; Cherif, Chokri; Bellmann, C

    2011-04-01

    We investigated morphology and wetting properties of textiles modified by chemically immobilized amphiphilic micrometer and submicrometer large Janus particles. The Janus particles bind by their reactive side to the textile surface, while their hydrophobic side faces the environment. It was found that the character of immobilization of the Janus particles on textile depends on their size: larger particles bind between fibers, while smaller ones bind to the fiber surface. In both cases, immobilization of Janus particles results in the hydrophobization of the hydrophilic textile surface. Finally, we demonstrated that submicrometer large Janus particles are very efficient for the design of water-repellent textiles. PMID:21366338

  1. Mobilization and biodegradation of 2-methylnaphthalene by amphiphilic polyurethane nano-particle.

    Science.gov (United States)

    Kim, Young-Bum; Kim, Ju-Young; Kim, Eun-ki

    2009-10-01

    Amphiphilic polyurethane (APU) nano-particle enhanced the mobilization of 2-methylnaphthalene (2-MNPT) in soil. Significant increase in the solubility of 2-MNPT was achieved. The molar solubilization ratio was 0.4 (mole 2-MNPT/mole APU). Simple precipitation of APU particle by 2 N CaCl(2) recovered 95% of APU particle and 92% of 2-MNPT simultaneously. Also, 2-MNPT, which was entrapped inside the APU particle, was directly degraded by Acinetobacter sp. as same efficiency as without APU particle. These results showed the potentials of APU particle in the mobilization and biodegradation of hydrophobic compounds from soil. PMID:19214790

  2. Glucagon-like peptide 1 receptor agonist (GLP-1 RA)

    DEFF Research Database (Denmark)

    von Scholten, Bernt Johan; Hansen, Tine Willum; Goetze, Jens Peter;

    2015-01-01

    AIMS: In a short-term study including 31 patients with type 2 diabetes, glucagon-like peptide 1 receptor agonist (GLP-1 RA) treatment was associated with a significant reversible decline in GFR. Twenty-three patients re-initiated GLP-1 RA treatment after the primary study, and the aim was to...

  3. Effect of the amino acid composition of cyclic peptides on their self-assembly in lipid bilayers.

    Science.gov (United States)

    Danial, Maarten; Perrier, Sébastien; Jolliffe, Katrina A

    2015-02-28

    The effect of amino acid composition on the formation of transmembrane channels in lipid bilayers upon self-assembly of alt-(L,D)-α-cyclic octapeptides has been investigated. Cyclic peptides comprising D-leucine, alternating with different combinations of L-azidolysine, L-lysine(Alloc), L-lysine and L-tryptophan were synthesized and the size of pores formed via self-assembly of these molecules in lipid bilayers was elucidated using large unilamellar vesicle fluorescence assays and dynamic light scattering. Pore formation was examined in large unilamellar vesicles made up of egg yolk phosphatidylcholine or Escherichia coli total lipid extract. From these analyses, we have established that cyclic peptides with charged side chains form large pores while those with neutral side chains form unimeric pores. Furthermore, the cyclic peptides that consist of non-symmetric amino acid configurations possess a higher membrane activity than the cyclic peptides with a symmetric amino acid configuration. In addition, we have found that peptide amphiphilicity plays a vital role in selective partitioning between bilayers that consist of egg yolk phosphatidylcholine and those comprised of E. coli total lipid extract. These results suggest that selective transbilayer channel formation via self-assembly may be a viable alternative for many applications that currently use more expensive, multistep synthesis methods. PMID:25566760

  4. Detergent-Like Activity and α-Helical Structure of Warnericin RK, an Anti-Legionella Peptide

    Science.gov (United States)

    Verdon, Julien; Falge, Mirjam; Maier, Elke; Bruhn, Heike; Steinert, Michael; Faber, Cornelius; Benz, Roland; Héchard, Yann

    2009-01-01

    Abstract Warnericin RK is the first antimicrobial peptide known to be active against Legionella pneumophila, a pathogen bacterium that is responsible for severe pneumonia. Strikingly, this peptide displays a very narrow range of antimicrobial activity, almost limited to the Legionella genus, and a hemolytic activity. A similar activity has been described for δ-lysin, a well-known hemolytic peptide of Staphylococci that has not been described as antimicrobial. In this study we aimed to understand the mode of action of warnericin RK and to explain its particular target specificity. We found that warnericin RK permeabilizes artificial membranes in a voltage-independent manner. Osmotic protection experiments on erythrocytes showed that warnericin RK does not form well-defined pores, suggesting a detergent-like mode of action, as previously described for δ-lysin at high concentrations. Warnericin RK also permeabilized Legionella cells, and these cells displayed a high sensitivity to detergents. Depending on the detergent used, Legionella was from 10- to 1000-fold more sensitive than the other bacteria tested. Finally, the structure of warnericin RK was investigated by means of circular dichroism and NMR spectroscopy. The peptide adopted an amphiphilic α-helical structure, consistent with the proposed mode of action. We conclude that the specificity of warnericin RK toward Legionella results from both the detergent-like mode of action of the peptide and the high sensitivity of these bacteria to detergents. PMID:19804724

  5. Fibrils from designed non-amyloid-related synthetic peptides induce AA-amyloidosis during inflammation in an animal model.

    Directory of Open Access Journals (Sweden)

    Per Westermark

    Full Text Available BACKGROUND: Mouse AA-amyloidosis is a transmissible disease by a prion-like mechanism where amyloid fibrils act by seeding. Synthetic peptides with no amyloid relationship can assemble into amyloid-like fibrils and these may have seeding capacity for amyloid proteins. PRINCIPAL FINDINGS: Several synthetic peptides, designed for nanotechnology, have been examined for their ability to produce fibrils with Congo red affinity and concomitant green birefringence, affinity for thioflavin S and to accelerate AA-amyloidosis in mice. It is shown that some amphiphilic fibril-forming peptides not only produced Congo red birefringence and showed affinity for thioflavin S, but they also shortened the lag phase for systemic AA-amyloidosis in mice when they were given intravenously at the time of inflammatory induction with silver nitride. Peptides, not forming amyloid-like fibrils, did not have such properties. CONCLUSIONS: These observations should caution researchers and those who work with synthetic peptides and their derivatives to be aware of the potential health concerns.

  6. Self-Assembled ROS-Sensitive Polymer-Peptide Therapeutics Incorporating Built-in Reporters for Evaluation of Treatment Efficacy.

    Science.gov (United States)

    Qiao, Zeng-Ying; Zhao, Wen-Jing; Cong, Yong; Zhang, Di; Hu, Zhiyuan; Duan, Zhong-Yu; Wang, Hao

    2016-05-01

    One of the major challenges in current cancer therapy is to maximize therapeutic effect and evaluate tumor progression under the scheduled treatment protocol. To address these challenges, we synthesized the cytotoxic peptide (KLAKLAK)2 (named KLAK) conjugated amphiphilic poly(β-thioester)s copolymers (H-P-K) composed of reactive oxygen species (ROS) sensitive backbones and hydrophilic polyethylene glycol (PEG) side chains. H-P-K could self-assemble into micelle-like nanoparticles by hydrophobic interaction with copolymer backbones as cores and PEG and KLAK as shells. The assembled polymer-peptide nanoparticles remarkably improved cellular internalization and accumulation of therapeutic KLAK in cells. Compared to free KLAK peptide, the antitumor activity of H-P-K was significantly enhanced up to ∼400 times, suggesting the effectiveness of the nanoscaled polymer-peptide conjugation as biopharmaceuticals. The higher antitumor activity of nanoparticles was attributed to the efficient disruption of mitochondrial membranes and subsequent excessive ROS production in cells. To realize the ROS monitoring and treatment evaluation, we encapsulated squaraine (SQ) dyes as built-in reporters in ROS-sensitive H-P-K micelles. The overgenerated ROS around mitochondria stimulated the swelling of nanoparticles and subsequent release of SQ, which formed H-aggregates and significantly increased the photoacoustic (PA) signal. We believed that this self-assembled polymer-peptide nanotherapeutics incorporating built-in reporters has great potential for high antitumor performance and in situ treatment evaluation. PMID:27023216

  7. Photoperiod Regulates vgf-Derived Peptide Processing in Siberian Hamsters.

    Directory of Open Access Journals (Sweden)

    Barbara Noli

    Full Text Available VGF mRNA is induced in specific hypothalamic areas of the Siberian hamster upon exposure to short photoperiods, which is associated with a seasonal decrease in appetite and weight loss. Processing of VGF generates multiple bioactive peptides, so the objective of this study was to determine the profile of the VGF-derived peptides in the brain, pituitary and plasma from Siberian hamsters, and to establish whether differential processing might occur in the short day lean state versus long day fat. Antisera against short sequences at the C- or N- termini of proVGF, as well as against NERP-1, TPGH and TLQP peptides, were used for analyses of tissues, and both immunohistochemistry and enzyme linked immunosorbent assay (ELISA coupled with high-performance liquid (HPLC or gel chromatography were carried out. VGF peptide immunoreactivity was found within cortex cholinergic perikarya, in multiple hypothalamic nuclei, including those containing vasopressin, and in pituitary gonadotrophs. ELISA revealed that exposure to short day photoperiod led to a down-regulation of VGF immunoreactivity in the cortex, and a less pronounced decrease in the hypothalamus and pituitary, while the plasma VGF levels were not affected by the photoperiod. HPLC and gel chromatography both confirmed the presence of multiple VGF-derived peptides in these tissues, while gel chromatography showed the presence of the VGF precursor in all tissues tested except for the cortex. These observations are consistent with the view that VGF-derived peptides have pleiotropic actions related to changing photoperiod, possibly by regulating cholinergic systems in the cortex, vasopressin hypothalamic pathways, and the reproductive axis.

  8. The coordination of unprotonated peptide tertiary structure as a metric of pMHC-TCR functional avidity.

    Science.gov (United States)

    Antipas, Georgios S E; Germenis, Anastasios E

    2015-12-01

    The coordination difference between the unprotonated tertiary structures of a native (Tax) peptide and a number of its variants - all peptides presented by HLA-A201 and bound to the human A6 T cell receptor-was discovered to constitute a metric of pMHC-TCR functional avidity. Moreover, increasing coordination deviations from the index were found to flag correspondingly weakening immunological outcomes of the variant peptides. The prognostic utility of the coordination difference of unprotonated tertiary structure was established to operate strictly on the peptide scale, seizing to be of relevance either to the immediate peptide environment (i.e. within the realm of peptide short range order, within 7 Å of any peptide atom) or over the entirety of the pMHC-TCR complex. Additionally, the imprint of peptide immunological identity was expressed both by the total coordination as well as by its C-C partial. PMID:26568977

  9. The coordination of unprotonated peptide tertiary structure as a metric of pMHC–TCR functional avidity

    Directory of Open Access Journals (Sweden)

    Georgios S.E. Antipas

    2015-12-01

    Full Text Available The coordination difference between the unprotonated tertiary structures of a native (Tax peptide and a number of its variants – all peptides presented by HLA-A201 and bound to the human A6 T cell receptor-was discovered to constitute a metric of pMHC–TCR functional avidity. Moreover, increasing coordination deviations from the index were found to flag correspondingly weakening immunological outcomes of the variant peptides. The prognostic utility of the coordination difference of unprotonated tertiary structure was established to operate strictly on the peptide scale, seizing to be of relevance either to the immediate peptide environment (i.e. within the realm of peptide short range order, within 7 Å of any peptide atom or over the entirety of the pMHC–TCR complex. Additionally, the imprint of peptide immunological identity was expressed both by the total coordination as well as by its C–C partial.

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

    Science.gov (United States)

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

    2014-01-01

    The therapeutic potential of α-helical anti-microbial peptides (AH-AMP) to combat pathogens is fast gaining prominence. Based on recently published open access software for characterizing α-helical peptides (PAGAL), we elucidate a search methodology (SCALPEL) that leverages the massive structural data pre-existing in the PDB database to obtain AH-AMPs belonging to the host proteome. We provide in vitro validation of SCALPEL on plant pathogens ( Xylella fastidiosa, Xanthomonas arboricola and Liberibacter crescens) by identifying AH-AMPs that mirror the function and properties of cecropin B, a well-studied AH-AMP. The identified peptides include a linear AH-AMP present within the existing structure of phosphoenolpyruvate carboxylase (PPC20), and an AH-AMP mimicing the properties of the two α-helices of cecropin B from chitinase (CHITI25). The minimum inhibitory concentration of these peptides are comparable to that of cecropin B, while anionic peptides used as control failed to show any inhibitory effect on these pathogens. Substitute therapies in place of conventional chemotherapies using membrane permeabilizing peptides like these might also prove effective to target cancer cells. The use of native structures from the same organism could possibly ensure that administration of such peptides will be better tolerated and not elicit an adverse immune response. We suggest a similar approach to target Ebola epitopes, enumerated using PAGAL recently, by selecting suitable peptides from the human proteome, especially in wake of recent reports of cationic amphiphiles inhibiting virus entry and infection. PMID:26629331

  11. NMR investigations of the conformation of new cyclodextrin-based amphiphilic transporters for hydrophobic drugs: molecular lollipops

    Science.gov (United States)

    Bellanger, Nathalie; Perly, Bruno

    1992-10-01

    Amphiphilic compounds, obtained by grafting aliphatic acids onto a modified cyclodextrin, have been synthesized and studied by solution NMR. The large chain-length dependence of the NMR spectra in aqueous media is explained by the possible formation of auto-inclusion complexes. This process has been evidenced by extensive NMR experiments and by competition with potential guests. This new class of molecules ("lollipops") provides important information for the optimization of a design for amphiphilic transporters to be included in organized phases such as micelles or liposomes.

  12. Biochemical functionalization of peptide nanotubes with phage displayed peptides

    Science.gov (United States)

    Swaminathan, Swathi; Cui, Yue

    2016-09-01

    The development of a general approach for the biochemical functionalization of peptide nanotubes (PNTs) could open up existing opportunities in both fundamental studies as well as a variety of applications. PNTs are spontaneously assembled organic nanostructures made from peptides. Phage display has emerged as a powerful approach for identifying selective peptide binding motifs. Here, we demonstrate for the first time the biochemical functionalization of PNTs via peptides identified from a phage display peptide library. The phage-displayed peptides are shown to recognize PNTs. These advances further allow for the development of bifunctional peptides for the capture of bacteria and the self-assembly of silver particles onto PNTs. We anticipate that these results could provide significant opportunities for using PNTs in both fundamental studies and practical applications, including sensors and biosensors nanoelectronics, energy storage devices, drug delivery, and tissue engineering.

  13. Peptide iodination on phenylalanine residues

    International Nuclear Information System (INIS)

    Peptide labelling with radioactive isotopes is always a compromise between peptide chemistry, labelling chemistry, and biological receptor tolerance. Therefore new ways for isotope introduction are always useful. The present contribution describes the introduction of iodine isotopes onto synthetic polypeptides by means of the Gattermann/ Sandmeyer reactions. Peptides containing the nitrophenylalanyl residue are reduced to the corresponding aminophenylalanyl, diazolized to the diazonium phenylalanyl peptide and converted to the iodophenylalanyl peptide in the presence of copper. Two examples are presented: angiotensin II and enkephalin. In both cases, the iodophenylalanyl residue is well accepted by the biological target. (author). 13 refs.; 4 figs

  14. Progress in developing amphiphilic cyclodextrin-based nanodevices for drug delivery.

    Science.gov (United States)

    Yaméogo, Josias B G; Géze, Annabelle; Choisnard, Luc; Putaux, Jean-Luc; Semdé, Rasmané; Wouessidjewe, Denis

    2014-01-01

    Nowadays, colloidal drug carriers represent an alternative to solve drug bioavailabily problems. During the past two decades, colloidal drug carriers have proved to improve the therapeutic index of drugs and thus increase their efficacy and/or reduce their toxicity. However, the major challenge in the development of these drug carriers remains the search for materials able to self-organize into stable nanoscale systems. In particular, amphiphilic α-, β- and γ-cyclodextrins (CDs), grafted on their secondary or primary side with different aliphatic chains, have been investigated as drug delivery vehicles due to their ability to self-assemble and form various stable colloidal systems such as micellar aggregates, nanoreservoirs or nanoparticles exhibiting a matricial, multilamellar or hexagonal supramolecular organization. These self-assembled CD-based nanodevices show some advantages in terms of stability, good ability to associate lipophilic drugs and good in vivo tolerance. This review focuses on the potential of the structured nanoparticles obtained from nonionic amphiphilic CDs in drug delivery and targeting. We discuss the synthesis and characterization of the building blocks as well as the preparation and characterization of colloidal particles made from these materials. We also considered some pharmaceutical applications and identified opportunities for an optimum use of this CD-based nanotechnology approach in addressing worldwide priority health problems. PMID:24354667

  15. Removal of volatile organic compounds using amphiphilic cyclodextrin-coated polypropylene

    Directory of Open Access Journals (Sweden)

    Ludmilla Lumholdt

    2014-11-01

    Full Text Available Polypropylene nonwovens were functionalised using a self-assembled, amphiphilic cyclodextrin coating and the potential for water purification by removal of pollutants was studied. As benzene is one of the problematic compounds in the Water Framework Directive, six volatile organic compounds (benzene and five benzene-based substances were chosen as model compounds. The compounds were tested as a mixture in order to provide a more realistic situation since the wastewater will be a complex mixture containing multiple pollutants. The volatile organic compounds are known to form stable inclusion complexes with cyclodextrins. Six different amphiphilic cyclodextrin derivatives were synthesised in order to elucidate whether or not the uptake abilities of the coating depend on the structure of the derivative. Headspace gas chromatography was used for quantification of the uptake exploiting the volatile nature of benzene and its derivatives. The capacity was shown to increase beyond the expected stoichiometries of guest–host complexes with ratios of up to 16:1.

  16. Amphiphilic nanocapsules entangled with organometallic coordination polymers for controlled cargo release.

    Science.gov (United States)

    Liang, Guodong; Ni, Huan; Bao, Suping; Zhu, Fangming; Gao, Haiyang; Wu, Qing; Tang, Ben Zhong

    2014-06-01

    A class of new amphiphilic nanocapsules entangled with organometallic coordination polymers has been developed for the first time. Poly(2-(N,N-dimethyl amino)ethyl methacrylate)-b-polystyrene capped with β-cyclodextrin (β-CD) (CD-PDMAEMA-b-PS) is first synthesized using sequent RAFT polymerization of styrene and 2-(N,N-dimethyl amino)ethyl methacrylate with xanthate modified β-CD as chain transfer agent. The end group of β-CD is allowed to include 4,4'-bipyridine through host-guest inclusion to yield PDMAEMA-b-PS terminated with an inclusion complex of β-CD and bipyridine (bpy-PDMAEMA-b-PS), which is then used as surfactant to prepare emulsion droplets in toluene/water mixture. Upon addition of Ni(II), bipyridine coordinates with Ni(II) to form coordination polymers in the periphery of emulsion droplets, affording amphiphilic capsules entangled with organometallic coordination polymers, as confirmed by GPC, (1)H NMR, SEM, TEM, DLS, and so on. The organometallic coordination polymer capsules are capable of encapsulating organic cargoes. Interestingly, encapsulated cargoes can be extracted from the capsules without damaging the capsules. Such capsules are potential candidates for encapsulating and controlled release of organic cargoes. PMID:24828951

  17. THE AMPHIPHILIC MULTIARM COPOLYMERS BASED ON HYPERBRANCHED POLYESTER AND LYSINE: SYNTHESIS AND SELF-ASSEMBLY

    Institute of Scientific and Technical Information of China (English)

    Jing Wang; Yuan Yao; Bing Ji; Wei Huang; Yong-feng Zhou; De-yue Yan

    2011-01-01

    The amphiphilic multiarm copolymers were synthesized through the modification of commercially available hyperbranched polyesters (Boltom H40) with N-ε-carbobenzoxy-L-Lysine N-carboxyanhydride (ZLys-NCA). After being condensed with N-Boc-phenylalanine (Boc-NPhe) and deprotected the Boc-groups in trifluoroacetic acid (TFA), the original terminal hydroxyl groups were transformed into the amino groups and then initiated the ring-opening polymerization of ZLys-NCA. The hydrophilic poly(L-lysine) was grafted to the surface of Boltorn H40 successfully after the protecting benzyl groups were removed by the HBr solution in glacial acetic acid (33 wt%). The resulting multiarm copolymers were characterized by the 1H-NMR, GPC and FTIR. The arm length calculated by NMR and GPC analysis was about 3 and 13 lysine-units for H40-Phe-PLysl and H40-Phe-PLys2 respectively. Due to the amphiphilic molecular structure, they displayed ability to self-assemble into spherical micelles in aqueous solution with the average diameter in the range from 70 nm to 250 nm. The CMC of H40-Phe-PLysl and H40-Phe-PLys2 was 0.013 mg/mL and 0.028 mg/mL, respectively,indicating that H40-Phe-PLysl with shorter arm length is easier to self-assemble than H40-Phe-PLys2 with longer arm length.

  18. Synthesis of an amphiphilic rhodamine derivative and characterization of its solution and thin film properties

    International Nuclear Information System (INIS)

    Here we present characterization of solution and thin film properties of Lissamine rhodamine B sulfonyl didodecyl amine (LRSD), an amphiphilic derivative of rhodamine. LRSD was synthesized by functionalizing Lissamine rhodamine B sulfonyl chloride (LRSC) with didodecylamine via a straightforward sulfonylation reaction. LRSD's long alkane chains make it highly soluble in chloroform, with a marked increase in brightness compared to the starting material. LRSD is shown to form well-defined robust micelles in water, without the addition of a co-surfactant and stable monolayers at the air–water interface. The greater lipophilicity of LRSD also enables doping into non-polar polymeric host matrices such as polystyrene with less aggregation and hence higher fluorescence quantum yield than LRSC or even rhodamine B. The monolayers of LRSD were prepared via Langmuir–Blodgett deposition and showed shifts in the photoluminescence peak from 575 nm to 595 nm, as the surface pressure is varied from 3 mN/m to 11 mN/m. - Highlights: • Lissamine rhodamine B sulfonyl didodecyl amine (LRSD) is soluble in chloroform. • LRSD shows robust quantum yield in solution and as a dopant in thin film. • LRSD is an amphiphilic rhodamine dye that forms compact fluorescent micelles. • LRSD forms a stable isotherm when spread at the air–water interface

  19. NOVEL AMPHIPHILIC FLUORESCENT GRAFT COPOLYMER: SYNTHESIS,CHARACTERIZATION AND ENCAPSULATION OF A HYDROPHOBIC AGENT

    Institute of Scientific and Technical Information of China (English)

    Zhao-qiang Wu; Shu Yang; Wen-yan Liao; Ling-zhi Meng

    2006-01-01

    Novel amphiphilic fluorescent graft copolymer (PVP-PyAHy) was successfully synthesized by the free radical copolymerization of hydrophobic monomer N-(1-pyrenebutyryl)-N'-acryloyl hydrazide (PyAHy) with hydrophilic precursor polymers of vinyl-functionalized poly(N-vinylpyrrolidone) (PVP) in DMF. The copolymer is amphiphilic and has intrinsic fluorescence. FT-IR, 1H-NMR, TEM, gel permeation chromatography-multi-angle laser light scattering, UV-Vis spectroscopy and fluorescence spectroscopy were used to characterize this copolymer. The TEM observation shows that the copolymer PVP-PyAHy forms micelles in aqueous solution. Results of fluorometric measurements illustrate that the critical micelle concentration (CMC) value of PVP-PyAHy in aqueous solution is about 0.90 mg/mL. To examine the encapsulation ability of the copolymer in aqueous media, methyl yellow was employed as a model hydrophobic agent. The loading level of the polymer to methyl yellow is 8.8 mg/g. The cytotoxicity assays for Madin Darby Canine Kidney (MDCK) cells shows good biocompatibility of PVP-PyAHy in vitro. These results suggest the potential of this copolymer PVP-PyAHy as drugs delivery carrier and fluorescent tracer.

  20. Hydrophobic cotton textile surfaces using an amphiphilic graphene oxide (GO) coating

    Science.gov (United States)

    Tissera, Nadeeka D.; Wijesena, Ruchira N.; Perera, J. Rangana; de Silva, K. M. Nalin; Amaratunge, Gehan A. J.

    2015-01-01

    We report for the first time hydrophobic properties on cotton fabric successfully achieved by grafting graphene oxide on the fabric surface, using a dyeing method. Graphite oxide synthesized by oxidizing natural flake graphite employing improved Hummer's method showed an inter layer spacing of ∼1 nm from XRD. Synthesized graphite oxide was exfoliated in water using ultrasound energy to obtain graphene oxide (GO). AFM data obtained for the graphene oxide dispersed in an aqueous medium revealed a non-uniform size distribution. FTIR characterization of the synthesized GO sheets showed both hydrophilic and hydrophobic functional groups present on the nano sheets giving them an amphiphilic property. GO flakes of different sizes were successfully grafted on to a cotton fabric surface using a dip dry method. Loading different amounts of graphene oxide on the cotton fiber surface allowed the fabric to demonstrate different degrees of hydrophobicity. The highest observed water contact angle was at 143° with the highest loading of graphene oxide. The fabric surfaces grafted with GO also exhibits adhesive type hydrophobicity. Microscopic characterization of the fiber surface using SEM and AFM reveals the deposition of GO sheets on the fiber surface as a conformal coating. Analysis of the fabric surface using UV-vis absorption allowed identification of the ratio of hydrophobic to hydrophilic domains present on the GO coated cotton fabric surface. Hydrophobic properties on cotton fabric are ascribed to two dimensional amphiphilic properties of deposited GO nano sheets, which successfully lower the interfacial energy of the fabric surface.