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Biopolymers

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https://www.readbyqxmd.com/read/28948603/process-development-of-a-fgf21-protein-antibody-conjugate
#1
Anouk Dirksen, Keith A Davis, Joe T Collins, Keshab Bhattacharya, Jari I Finneman, Erin L Pepin, Jeffrey S Ryczek, Paul W Brown, William B Wellborn, Ratish Mangalathillam, Brad P Evans, Mark J Pozzo, Rory F Finn
A scalable, viable process was developed for the Fibroblast Growth Factor 21 (FGF21) protein-antibody conjugate, CVX-343, an extended half-life therapeutic for the treatment of metabolic disease. CVX-343 utilizes the CovX antibody scaffold technology platform that was specifically developed for peptide and protein half-life extension. CVX-343 is representative of a growing number of complex novel peptide- and protein-based bioconjugate molecules currently being explored as therapeutic candidates. The complexity of these bioconjugates, assembled using well-established chemistries, can lead to very difficult production schemes requiring multiple starting materials and a combination of diverse technologies...
September 26, 2017: Biopolymers
https://www.readbyqxmd.com/read/28944959/antimicrobial-activity-of-lysozyme-isoforms-key-molecular-features
#2
Melanie Derde, Véronique Vié, Astrid Walrant, Sandrine Sagan, Valérie Lechevalier, Catherine Guérin-Dubiard, Stéphane Pezennec, Marie-Françoise Cochet, Gilles Paboeuf, Maryvonne Pasco, Florence Baron, Michel Gautier, Sophie Jan, Françoise Nau
Increasing bacterial resistance towards antibiotics has stimulated research for novel antimicrobials. Proteins acting on bacterial membranes could be a solution. Lysozyme has been proven active against E. coli by disruption of both outer and cytoplasmic membranes, with dry-heating increasing lysozyme activity. Dry-heated lysozyme (DH-L) is a mixture of isoforms (isoaspartyl, native-like and succinimide lysozymes), giving rise to two questions: what effects does each form have, and which physicochemical properties are critical as regards the antibacterial activity? These issues were investigated by fractionating DH-L, analyzing structural properties of each fraction, and testing each fraction in vivo on bacteria and in vitro on membrane models...
September 25, 2017: Biopolymers
https://www.readbyqxmd.com/read/28925099/highly-efficiency-antibacterial-diblock-copolypeptides-based-on-lysine-and-phenylalanine
#3
Xiaokai Su, Xinyu Zhou, Zhengzhong Tan, Chuncai Zhou
A series of amphiphilic diblock copolypeptides (K30 -b-F15 , K30 -b-F30 , and K30 -b-F45 ) were synthesized via N-carboxy-α-amino-anhydride ring-opening polymerization. The copolypeptides had excellent antibacterial efficacy to both Gram positive (S. aureus) and Gram negative (E. coli) bacteria. The minimum inhibitory concentrations (MICs) against E. coli and S. aureus are 8 μg mL(-1) and 2 μg mL(-1) , respectively, lower than most natural and artificial antimicrobial peptides (AMPs). The morphological changes of the bacteria treated with diblock copolypeptides were investigated by transmission electron microscopy; the results proved that the diblock copolypeptides had a similar antibacterial pore-forming mechanism to natural cationic peptides...
September 19, 2017: Biopolymers
https://www.readbyqxmd.com/read/28925040/thermal-melt-circular-dichroism-spectroscopic-studies-for-identifying-stabilising-amphipathic-molecules-for-the-voltage-gated-sodium-channel-navms
#4
Sam M Ireland, Altin Sula, B A Wallace
Purified integral membrane proteins require amphipathic molecules to maintain their solubility in aqueous solutions. These complexes, in turn, are used in studies to characterise the protein structures by a variety of biophysical and structural techniques, including spectroscopy, crystallography, and cryo-electron microscopy. Typically the amphilphiles used have been detergent molecules, but more recently they have included amphipols, which are polymers of different sizes and compositions designed to create smaller, more well-defined solubilised forms of the membrane proteins...
September 19, 2017: Biopolymers
https://www.readbyqxmd.com/read/28922450/structural-insight-into-the-xtacc3-xmap215-interaction-from-cd-and-nmr-studies-on-model-peptides
#5
Angélica Partida-Hanon, Miguel A Treviño, Miguel Mompeán, Ma Ángeles Jiménez, Marta Bruix
TACC3 is a centrosomal adaptor protein that plays important roles during mitotic spindle assembly. It interacts with chTOG/XMAP215, which catalyzes the addition of tubulin dimers during microtubule growth. A 3D coiled-coil model for this interaction is available but the structural details are not well described. To characterize this interaction at atomic resolution, we have designed a simplified version of the system based on small peptides. Four different peptides have been studied by circular dichroism and nuclear magnetic resonance both singly and in all possible combinations; namely, five peptide pairs and two trios...
September 18, 2017: Biopolymers
https://www.readbyqxmd.com/read/28832933/synthesis-and-gelation-of-copolypept-o-ides-with-random-and-block-structure
#6
Yan Xiao, Jianqiang Wang, Jun Zhang, Andreas Heise, Meidong Lang
Copolypept(o)ides of polysarcosine (PSar) and poly(N-isopropyl-L-glutamine) (PIGA) with random and block sequence structures were synthesized by ring-opening polymerization (ROP) of sarcosine N-carboxyanhydrides (Sar-NCA) and γ-benzyl-l-glutamate N-carboxyanhydrides (BLG-NCA) and post modification. With different distribution of Sar along the main chain, H-bonding pattern and secondary structure of polypeptides were turned, as well as aggregation and gelation behavior. Both copolypept(o)ides formed hydrogels above their critical gelation concentrations (CGCs) without thermo-sensitivity, which was normally reserved for PEG copolypeptides (eg, PEG-b-PIGA)...
August 18, 2017: Biopolymers
https://www.readbyqxmd.com/read/28799649/design-of-modular-dual-enzyme-responsive-peptides
#7
Natalie Boehnke, Heather D Maynard
Dual enzyme-responsive peptides were synthesized by masking the ɛ-amine of lysine with various enzyme substrates. Enzymatic cleavage of these sequences unmasked the ɛ-amine, allowing for further digestion by a second enzyme, which was monitored colorimetrically. This modular peptide design should provide substrates for a large combination of clinically relevant enzymes.
September 2017: Biopolymers
https://www.readbyqxmd.com/read/28555880/fabrication-of-elastomeric-silk-fibers
#8
Sarah A Bradner, Benjamin P Partlow, Peggy Cebe, Fiorenzo G Omenetto, David L Kaplan
Methods to generate fibers from hydrogels, with control over mechanical properties, fiber diameter, and crystallinity, while retaining cytocompatibility and degradability, would expand options for biomaterials. Here, we exploited features of silk fibroin protein for the formation of tunable silk hydrogel fibers. The biological, chemical, and morphological features inherent to silk were combined with elastomeric properties gained through enzymatic crosslinking of the protein. Postprocessing via methanol and autoclaving provided tunable control of fiber features...
September 2017: Biopolymers
https://www.readbyqxmd.com/read/28547860/inhibition-of-melanoma-metastasis-by-dual-peptide-plga-nps
#9
Denise Costa Arruda, Thaís Dolzany de Oliveira, Patrícia Harume Fukuda Cursino, Vera Susana Carneiro Maia, Rodrigo Berzaghi, Luiz R Travassos, Dayane Batista Tada
Despite the positive results observed in vitro and in vivo, clinical trials with bioactive peptides are generally hampered by their fast degradation in the biological system. Two bioactive peptides, P20 (CSSRTMHHC) and the combined peptide C (CVNHPAFACGYGHTMYYHHYQHHL) have been identified as anticancer therapeutics. Combined peptide C consists of peptide C (CVNHPAFAC), a tumor-homing peptide, conjugated to the antiangiogenic peptide HTMYYHHYQHHL with a GYG. In this work, PLGA NPs with peptide C were applied as a dual-peptide carrier for application in cancer therapy...
September 2017: Biopolymers
https://www.readbyqxmd.com/read/28464209/alanine-scan-of-the-opioid-peptide-dynorphin-b-amide
#10
Anand A Joshi, Thomas F Murray, Jane V Aldrich
To date structure-activity relationship (SAR) studies of the dynorphins (Dyn), endogenous peptides for kappa opioid receptors (KOR), have focused almost exclusively on Dyn A with minimal studies on Dyn B. While both Dyn A and Dyn B have identical N-terminal sequences, their C-terminal sequences differ, which could result in differences in pharmacological activity. We performed an alanine scan of the non-glycine residues up through residue 11 of Dyn B amide to explore the roles of these side chains in the activity of Dyn B...
September 2017: Biopolymers
https://www.readbyqxmd.com/read/28459137/lysine-to-arginine-mutagenesis-of-chlorotoxin-enhances-its-cellular-uptake
#11
Paola G Ojeda, Sónia Troeira Henriques, Yijun Pan, Joseph A Nicolazzo, David J Craik, Conan K Wang
Chlorotoxin (CTX), a disulfide-rich peptide from the scorpion Leiurus quinquestriatus, has several promising biopharmaceutical properties, including preferential affinity for certain cancer cells, high serum stability, and cell penetration. These properties underpin its potential for use as a drug design scaffold, especially for the treatment of cancer; indeed, several analogs of CTX have reached clinical trials. Here, we focus on its ability to internalize into cells-a trait associated with a privileged subclass of peptides called cell-penetrating peptides-and whether it can be improved through conservative substitutions...
September 2017: Biopolymers
https://www.readbyqxmd.com/read/28509352/convergent-mechanisms-favor-fast-amyloid-formation-in-two-lambda-6a-ig-light-chain-mutants
#12
Gilberto Valdés-García, César Millán-Pacheco, Nina Pastor
Extracellular deposition as amyloids of immunoglobulin light chains causes light chain amyloidosis. Among the light chain families, lambda 6a is one of the most frequent in light chain amyloidosis patients. Its germline protein, 6aJL2, and point mutants, R24G and P7S, are good models to study fibrillogenesis, because their stability and fibril formation characteristics have been described. Both mutations make the germline protein unstable and speed up its ability to aggregate. To date, there is no molecular mechanism that explains how these differences in amyloidogenesis can arise from a single mutation...
August 2017: Biopolymers
https://www.readbyqxmd.com/read/28422272/modeling-interactions-between-a-%C3%AE-o-4-type-lignin-model-compound-and-1-allyl-3-methylimidazolium-chloride-ionic-liquid
#13
Youtao Zhu, Jing Yan, Chengbu Liu, Dongju Zhang
Aiming at understanding the molecular mechanism of the lignin dissolution in imidazolium-based ionic liquids (ILs), this work presents a combined quantum chemistry (QC) calculation and molecular dynamics (MD) simulation study on the interaction of the lignin model compound, veratrylglycerol-β-guaiacyl ether (VG) with 1-allyl-3-methylimidazolium chloride ([Amim]Cl). The monomer of VG is shown to feature a strong intramolecular hydrogen bond, and its dimer is indicated to present important π-π stacking and intermolecular hydrogen bonding interactions...
August 2017: Biopolymers
https://www.readbyqxmd.com/read/28387920/hydrophobic-hydrophilic-forces-in-protein-folding
#14
Stewart R Durell, Arieh Ben-Naim
The process of protein folding is obviously driven by forces exerted on the atoms of the amino-acid chain. These forces arise from interactions with other parts of the protein itself (direct forces), as well as from interactions with the solvent (solvent-induced forces). We present a statistical-mechanical formalism that describes both these direct and indirect, solvent-induced thermodynamic forces on groups of the protein. We focus on 2 kinds of protein groups, commonly referred to as hydrophobic and hydrophilic...
August 2017: Biopolymers
https://www.readbyqxmd.com/read/28741310/homo-and-heteropolymer-self-assembly-of-recombinant-trichocytic-keratins
#15
Rachael N Parker, Kristina L Roth, Christina Kim, Jennifer P McCord, Mark E Van Dyke, Tijana Z Grove
In the past two decades, keratin biomaterials have shown impressive results as scaffolds for tissue engineering, wound healing, and nerve regeneration. In addition to its intrinsic biocompatibility, keratin interacts with specific cell receptors eliciting beneficial biochemical cues. However, during extraction from natural sources, such as hair and wool fibers, natural keratins are subject to extensive processing conditions that lead to formation of unwanted by-products. Additionally, natural keratins suffer from limited sequence tunability...
July 24, 2017: Biopolymers
https://www.readbyqxmd.com/read/28734076/ensemble-characterization-of-an-intrinsically-disordered-fg-nup-peptide-and-its-f-a-mutant-in-dmso-d6
#16
Korey M Reid, Punnepalli Sunanda, S Raghothama, V V Krishnan
Intrinsically disordered proteins (IDP) lack a well-defined 3D-structure under physiological conditions, yet, the inherent disorder represented by an ensemble of conformation plays a critical role in many cellular and regulatory processes. Nucleoporins, or Nups, are the proteins found in the nuclear pore complex (NPC). The central pore of the NPC is occupied by Nups, which have phenylalanine-glycine domain repeats and are intrinsically disordered, and therefore are termed FG-Nups. These FG-domain repeats exhibit differing cohesiveness character and differ from least (FG) to most (GLFG) cohesive...
July 22, 2017: Biopolymers
https://www.readbyqxmd.com/read/28085180/log-d-versus-hplc-derived-hydrophobicity-the-development-of-predictive-tools-to-aid-in-the-rational-design-of-bioactive-peptoids
#17
H L Bolt, C E J Williams, R V Brooks, R N Zuckermann, S L Cobb, E H C Bromley
Hydrophobicity has proven to be an extremely useful parameter in small molecule drug discovery programmes given that it can be used as a predictive tool to enable rational design. For larger molecules, including peptoids, where folding is possible, the situation is more complicated and the average hydrophobicity (as determined by RP-HPLC retention time) may not always provide an effective predictive tool for rational design. Herein, we report the first ever application of partitioning experiments to determine the log D values for a series of peptoids...
July 2017: Biopolymers
https://www.readbyqxmd.com/read/28608428/fusion-of-plectasin-derivative-nz2114-with-hydrophilic-random-coil-polypeptide-recombinant-production-in-pichia-pastoris-and-antimicrobial-activity-against-clinical-strain-mrsa
#18
L A Lima, R de Vries, L S Biswaro, I M Vasconcelos, O L Franco, S C Dias
One of the roadblocks towards the practical use of antimicrobial peptides for medical use is their relatively high cost when synthesized chemically. Effective recombinant production has only been successful in some cases, such as the previously reported production in Pichia pastoris of the antimicrobial plectasin derivative peptide NZ2114. The same production host has also been used extensively to produce so-called protein-polymers: sequences that consist of repetitions of simple amino acid motifs found in structural proteins such as collagen and elastin, and that can be designed to self-assemble in micelles, fibers and hydrogels...
June 12, 2017: Biopolymers
https://www.readbyqxmd.com/read/28589640/self-assembly-of-t-butyloxycarbonyl-protected-dipeptide-methyl-esters-composed-of-leucine-isoleucine-and-valine-into-highly-organized-structures-from-alcohol-and-aqueous-alcohol-mixtures
#19
Chivukula Subbalakshmi, Pratyay Basak, Ramakrishnan Nagaraj
Short peptides composed of phenylalanine and sequences derived from amyloidogenic peptides have the ability to self-assemble to form nanostructures including hydrogels. The self-assembly of peptides composed of only hydrophobic amino acids and aliphatic protecting groups have not been investigated in detail. We have examined various aspects of nanostructures formed by N-terminal t-butyloxycarbonyl-protected aliphatic dipeptide methyl esters dissolved in various solvents. Scanning electron microscopic images indicate that depending on the sequence, position of the amino acid and solvent of dissolution, the peptides self-assemble into superstructures such as nanotubes and needles particularly from aqueous mixtures of organic solvents...
June 7, 2017: Biopolymers
https://www.readbyqxmd.com/read/28224610/structural-changes-in-cartilage-and-collagen-studied-by-high-temperature-raman-spectroscopy
#20
Mark Fields, Nicholas Spencer, Jayesh Dudhia, Paul F McMillan
Understanding the high temperature behavior of collagen and collagenous tissue is important for surgical procedures and biomaterials processing for the food, pharmaceutical, and cosmetics industries. One primary event for proteins is thermal denaturation that involves unfolding the polypeptide chains while maintaining the primary structure intact. Collagen in the extracellular matrix of cartilage and other connective tissue is a hierarchical material containing bundles of triple-helical fibers associated with water and proteoglycan components...
June 2017: Biopolymers
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