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Ion transport is essential to energy storage, cellular signalling and desalination. Polymers have been explored for decades as solid-state electrolytes by either adding salt to polar polymers or tethering ions to the backbone to create less flammable and more robust systems. New design paradigms are needed to advance the performance of solid polymer electrolytes beyond conventional systems. Here the role of a helical secondary structure is shown to greatly enhance the conductivity of solvent-free polymer electrolytes using cationic polypeptides with a mobile anion. Longer helices lead to higher conductivity, and random coil peptides show substantially lower conductivity. The macrodipole of the helix increases with peptide length, leading to larger dielectric constants. The hydrogen bonding of the helix also imparts thermal and electrochemical stability, while allowing for facile dissolution back to monomer in acid. Peptide polymer electrolytes present a promising platform for the design of next-generation ion-transporting materials.
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The biological significance of self-assembled protein filament networks and their unique mechanical properties have sparked interest in the development of synthetic filament networks that mimic these attributes. Building on the recent advancement of autoaccelerated ring-opening polymerization of amino acid N-carboxyanhydrides (NCAs), this study strategically explores a series of random copolymers comprising multiple amino acids, aiming to elucidate the core principles governing gelation pathways of these purpose-designed copolypeptides. Utilizing glutamate (Glu) as the primary component of copolypeptides, two targeted pathways were pursued: first, achieving a fast fibrillation rate with lower interaction potential using serine (Ser) as a comonomer, facilitating the creation of homogeneous fibril networks; and second, creating more rigid networks of fibril clusters by incorporating alanine (Ala) and valine (Val) as comonomers. The selection of amino acids played a pivotal role in steering both the morphology of fibril superstructures and their assembly kinetics, subsequently determining their potential to form sample-spanning networks. Importantly, the viscoelastic properties of the resulting supramolecular hydrogels can be tailored according to the specific copolypeptide composition through modulations in filament densities and lengths. The findings enhance our understanding of directed self-assembly in high molecular weight synthetic copolypeptides, offering valuable insights for the development of synthetic fibrous networks and biomimetic supramolecular materials with custom-designed properties.
Assuntos
Hidrogéis , Peptídeos , Hidrogéis/química , Peptídeos/química , Aminoácidos , Ácido Glutâmico/química , Alanina/químicaRESUMO
BACKGROUND: Iron deficiency anemia (IDA) is one of the commonest global nutritional deficiency diseases, and the low bioavailability of iron is a key contributing factor. The peptide-iron complex could be used as a novel iron supplement to improve iron bioavailability. RESULTS: In this study, antioxidant low molecular weight (<3 kDa) phosvitin peptide (named PP-4) was separated to prepare a phosvitin peptide-ferrous complex (named PP-4-Fe); then the structural conformation of PP-4-Fe was characterized and its bioavailability by in vitro digestion was evaluated. The results showed that PP-4 had good ferrous-binding activity with 96.14 ± 2.86 µg Fe2+ mg-1 , and had a strong antioxidant effect with 995.61 ± 79.75 µmol TE mg-1 in 2,2'-azinobis'3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 62.3 ± 3.95 µmol FeSO4 mg-1 in ferric ion reducing antioxidant power (FRAP). After ferrous binding, the FRAP activity of PP-4-Fe, enhanced by 1.8 times, formed a more ordered structure with an increase in α-helix and decrease in γ-random coil. The ferrous binding sites of PP-4 involved were the amino, carboxyl, imidazole, and phosphate groups. The PP-4-Fe complex displayed excellent gastrointestinal stability and antioxidant effects during digestion. The iron dialysis percentage of PP-4-Fe was 74.59% ± 0.68%, and increased to 81.10% ± 0.89% with the addition of 0.25 times vitamin C (VC). This indicated that PP-4-Fe displayed excellent bioavailability and VC in sufficient quantities had a synergistic effect on improving bioavailability. CONCLUSIONS: This study demonstrated that antioxidant phosvitin peptide was an efficient delivery system to protect ferrous ions and suggested that the phosvitin peptide-ferrous complex has strong potential as a ferrous supplement. © 2023 Society of Chemical Industry.
Assuntos
Antioxidantes , Fosvitina , Antioxidantes/metabolismo , Fosvitina/metabolismo , Disponibilidade Biológica , Diálise Renal , Ferro/metabolismo , Ácido Ascórbico , Peptídeos/química , Compostos FerrososRESUMO
In cells, actin and tubulin polymerization is regulated by nucleation factors, which promote the nucleation and subsequent growth of protein filaments in a controlled manner. Mimicking this natural mechanism to control the supramolecular polymerization of macromolecular monomers by artificially created nucleation factors remains a largely unmet challenge. Biological nucleation factors act as molecular scaffolds to boost the local concentrations of protein monomers and facilitate the required conformational changes to accelerate the nucleation and subsequent polymerization. An accelerated assembly of synthetic poly(l-glutamic acid) into amyloid fibrils catalyzed by cationic silica nanoparticle clusters (NPCs) as artificial nucleation factors is demonstrated here and modeled as supramolecular polymerization with a surface-induced heterogeneous nucleation pathway. Kinetic studies of fibril growth coupled with mechanistic analysis demonstrate that the artificial nucleators predictably accelerate the supramolecular polymerization process by orders of magnitude (e.g., shortening the assembly time by more than 10 times) when compared to the uncatalyzed reaction, under otherwise identical conditions. Amyloid-like fibrillation was supported by a variety of standard characterization methods. Nucleation followed a Michaelis-Menten-like scheme for the cationic silica NPCs, while the corresponding anionic or neutral nanoparticles had no effect on fibrillation. This approach shows the effectiveness of charge-charge interactions and surface functionalities in facilitating the conformational change of macromolecular monomers and controlling the rates of nucleation for fibril growth. Molecular design approaches like these inspire the development of novel materials via biomimetic supramolecular polymerizations.
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Amiloide , Peptídeos , Amiloide/química , Proteínas Amiloidogênicas , Cinética , Peptídeos/química , PolimerizaçãoRESUMO
With PEG-like properties, such as hydrophilicity and stealth effect against protein absorption, oligo(ethylene glycol) (OEG)-functionalized polypeptides have emerged as a new class of biomaterials alternative to PEG with polypeptide-like properties. Synthesis of this class of materials, however, has been demonstrated very challenging, as the synthesis and purification of OEG-functionalized N-carboxyanhydrides (OEG-NCAs) in high purity, which is critical for the success in polymerization, is tedious and often results in low yield. OEG-functionalized polypeptides are therefore only accessible to a few limited labs with expertise in this specialized NCA chemistry and materials. Here, we report the controlled synthesis of OEG-functionalized polypeptides in high yield directly from the OEG-functionalized amino acids via easy and reproducible polymerization of non-purified OEG-NCAs. The prepared amphiphilic block copolypeptides can self-assemble into narrowly dispersed nanoparticles in water, which show properties suitable for drug delivery applications.
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Etilenoglicol , Peptídeos , Aminoácidos , Interações Hidrofóbicas e Hidrofílicas , PolimerizaçãoRESUMO
The recent advances in accelerated polymerization of N-carboxyanhydrides (NCAs) enriched the toolbox to prepare well-defined polypeptide materials. Herein we report the use of crown ether (CE) to catalyze the polymerization of NCA initiated by conventional primary amine initiators in solvents with low polarity and low hydrogen-bonding ability. The cyclic structure of the CE played a crucial role in the catalysis, with 18-crown-6 enabling the fastest polymerization kinetics. The fast polymerization kinetics outpaced common side reactions, enabling the preparation of well-defined polypeptides using an α-helical macroinitiator. Experimental results as well as the simulation methods suggested that CE changed the binding geometry between NCA and propagating amino chain-end, which promoted the molecular interactions and lowered the activation energy for ring-opening reactions of NCAs. This work not only provides an efficient strategy to prepare well-defined polypeptides with functionalized C-termini, but also guides the design of catalysts for NCA polymerization.
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Infections by intracellular pathogens are difficult to treat because of the poor accessibility of antibiotics to the pathogens encased by host cell membranes. As such, a strategy that can improve the membrane permeability of antibiotics would significantly increase their efficiency against the intracellular pathogens. Here, we report the design of an adaptive, metaphilic cell-penetrating polypeptide (CPP)-antibiotic conjugate (VPP-G) that can effectively eradicate the intracellular bacteria both in vitro and in vivo. VPP-G was synthesized by attaching vancomycin to a highly membrane-penetrative guanidinium-functionalized metaphilic CPP. VPP-G effectively kills not only extracellular but also far more challenging intracellular pathogens, such as S. aureus, methicillin-resistant S. aureus, and vancomycin-resistant Enterococci. VPP-G enters the host cell via a unique metaphilic membrane penetration mechanism and kills intracellular bacteria through disruption of both cell wall biosynthesis and membrane integrity. This dual antimicrobial mechanism of VPP-G prevents bacteria from developing drug resistance and could also potentially kill dormant intracellular bacteria. VPP-G effectively eradicates MRSA in vivo, significantly outperforming vancomycin, which represents one of the most effective intracellular antibacterial agents reported so far. This strategy can be easily adapted to develop other conjugates against different intracellular pathogens by attaching different antibiotics to these highly membrane-penetrative metaphilic CPPs.
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Ribozymes synthesize proteins in a highly regulated local environment to minimize side reactions caused by various competing species. In contrast, it is challenging to prepare synthetic polypeptides from the polymerization of N-carboxyanhydrides (NCAs) in the presence of water and impurities, which induce monomer degradations and chain terminations, respectively. Inspired by natural protein synthesis, we herein report the preparation of well-defined polypeptides in the presence of competing species, by using a water/dichloromethane biphasic system with macroinitiators anchored at the interface. The impurities are extracted into the aqueous phase in situ, and the localized macroinitiators allow for NCA polymerization at a rate which outpaces water-induced side reactions. Our polymerization strategy streamlines the process from amino acids toward high molecular weight polypeptides with low dispersity by circumventing the tedious NCA purification and the demands for air-free conditions, enabling low-cost, large-scale production of polypeptides that has potential to change the paradigm of polypeptide-based biomaterials.
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Aminoácidos/química , Anidridos/química , Peptídeos , Polimerização , Cinética , Cloreto de Metileno/química , Modelos Biológicos , Peso Molecular , Biossíntese Peptídica , Peptídeos/síntese química , Peptídeos/química , Água/químicaRESUMO
Multiblock copolypeptides have attracted broad interests because their potential to form ordered structures and possess protein-mimetic functions. Controlled synthesis of multiblock copolypeptides through the sequential addition of N-carboxyanhydrides (NCAs), especially with the block number higher than five, however, is challenging and rarely reported due to competing side reactions during the polymerization process. Herein we report the unprecedented synthesis of block copolypeptides with up to 20 blocks, enabled by ultrafast polypeptide chain propagation in a water/chloroform emulsion system that outpaces side reactions and ensures high end-group fidelity. Well-defined multiblock copolypeptides with desired block numbers, block lengths, and block sequences as well as very low dispersity were readily attainable in a few hours. This method paves the way for the fast production of a large number of sequence-regulated multiblock copolypeptide materials, which may exhibit interesting assembly behaviors and biomedical applications.