Recent Advances and Future Developments in the Preparation of Polypeptides via N-Carboxyanhydride (NCA) Ring-Opening Polymerization

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(35), С. 24189 - 24208

Опубликована: Авг. 22, 2024

Polypeptides have the same or similar backbone structures as proteins and peptides, rendering them suitable important biomaterials. Amino acid N-carboxyanhydrides (NCA) ring-opening polymerization has been most efficient strategy for polypeptide preparation, with continuous advance in design of initiators, catalysts reaction conditions. This Perspective first summarizes recent progress NCA synthesis purification. Subsequently, we focus on various initiators polymerization, accelerating enhancing controllability advances approach polymerization. Finally, discuss future research directions open challenges.

Язык: Английский

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Enhancing Antibiotic-Resistant Bacterial Infection Therapy: Self-Assembling Gemini Quaternary Ammonium-Functionalized Peptide Nanoassemblies with Multiple Antibacterial Mechanisms

ACS Nano, Год журнала: 2025, Номер unknown

Опубликована: Фев. 12, 2025

The rising threat of antimicrobial-resistant (AMR) infections highlights the urgent need for effective antimicrobial agents and therapies. Peptide-based nanomaterials are well-placed to meet this need. Here, we explore conjugation gemini quaternary ammonium compounds (GQAs) with designed short hexapeptides create cationic low cytotoxicity minimal resistance tendency. (WA)3GQA8C self-assembles into nanoparticles exhibits potent activity against drug-resistant pathogens enhanced stability. protects subcutaneous abscess infection rescues mice from acute peritonitis by reducing systemic bacterial burden alleviating organ damage, superior effects vancomycin. Notably, thoroughly disrupts membrane integrity akin peeling fruit induce disintegration, a feat inaccessible conventional antibiotics. Mechanistic studies suggest that targets phospholipids phosphatidylglycerol (PG), inducing PG deformation form fibrous or lamellar structures, which leads disruption membrane. Furthermore, interference in lipoprotein trafficking exacerbates damage integrity. also synergizes impairing protein synthesis function ribosome. These quaternized peptide nanoassemblies provide rational strategy designing peptide-based combat growing threats resistant bacteria.

Язык: Английский

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Combating bacterial infections with host defense peptides: Shifting focus from bacteria to host immunity

Drug Resistance Updates, Год журнала: 2023, Номер 72, С. 101030 - 101030

Опубликована: Ноя. 30, 2023

Язык: Английский

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Design and optimization of ε-poly-l-lysine with specific functions for diverse applications

International Journal of Biological Macromolecules, Год журнала: 2024, Номер 262, С. 129513 - 129513

Опубликована: Янв. 22, 2024

Язык: Английский

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Peptide-Mimicking Poly(2-oxazoline)s Possessing Potent Antifungal Activity and BBB Penetrating Property to Treat Invasive Infections and Meningitis

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(47), С. 25753 - 25765

Опубликована: Ноя. 15, 2023

Invasive fungal infections, including meningitis, cause a high mortality rate due to few available antifungal drugs and frequently associated side effects quick emergence of drug-resistant fungi. The restrictive permeability the blood–brain barrier (BBB) further limits efficacy agents substantially in treating meningitis. Hereby, we design synthesize guanidinium-functionalized poly(2-oxazoline)s by mimicking cell-penetrating peptides. optimal polymer, PGMeOx10 bearing methylene spacer arm, displays potent activities against fungi biofilm, negligible toxicity, insusceptibility antimicrobial resistance. Moreover, can break BBB retractions exert promising functions brain. demonstrates vivo therapeutic mouse models skin infection, systemic effectively rescues infected mice reduces burden inflammation These results excellent biosafety indicate effectiveness potential our strategy infections

Язык: Английский

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The choice of antimicrobial polymers: Hydrophilic or hydrophobic?

Chinese Chemical Letters, Год журнала: 2024, Номер 35(9), С. 109768 - 109768

Опубликована: Март 16, 2024

Язык: Английский

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Polysaccharide-based antibacterial nanocomposite hydrogels with Janus structure for treatment of infected extraction socket

Science China Materials, Год журнала: 2024, Номер 67(8), С. 2550 - 2557

Опубликована: Апрель 1, 2024

Язык: Английский

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Lysine aggregates‐based nanostructured antimicrobial peptides for cariogenic biofilm microenvironment‐activated caries treatment

Aggregate, Год журнала: 2024, Номер 5(5)

Опубликована: Апрель 30, 2024

Abstract Dental caries is one of the most prevalent and costly biofilm‐induced oral diseases that causes deterioration mineralized tooth tissue. Traditional antimicrobial agents like antibiotics peptides (AMPs) struggle to effectively eradicate bacteria in biofilms without eliciting resistance. Herein, we demonstrate construction FeOOH@Fe‐Lysine@Au nanostructured AMPs (nAMPs) distinguished by their AMP‐like antibacterial activity self‐producing reactive oxygen species (ROS) capacity for treatment. On hand, nAMPs can catalyze glucose oxidation generate ROS within cariogenic biofilm microenvironment, resulting disintegration extracellular polymeric substance matrix exposure bacteria. other attach bacterial surfaces via electrostatic attractions, proceeding damage membranes, disrupt metabolic pathways, inhibit protein synthesis through aggregated lysine generated ROS. Based on this mechanism, Streptococcus mutans its associated biofilm, significantly impeding progression dental caries. Given straightforward cost‐efficient preparation compared require specific sequences, minimal adverse impacts gingival/palatal tissues, major organs, oral/gut microbiomes, our research may promote development novel therapeutic health maintenance.

Язык: Английский

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Dual-function antimicrobial-antibiofilm peptide hybrid to tackle biofilm-forming Staphylococcus epidermidis

Annals of Clinical Microbiology and Antimicrobials, Год журнала: 2024, Номер 23(1)

Опубликована: Май 16, 2024

Abstract Background Due to their resistance and difficulty in treatment, biofilm-associated infections are problematic among hospitalized patients globally account for 60% of all bacterial humans. Antibiofilm peptides have recently emerged as an alternative treatment since they can be effectively designed exert a different mode biofilm inhibition eradication. Methods A novel antibiofilm peptide, BiF, was from the conserved sequence 18 α-helical by template-assisted technique its activity improved hybridization with lipid binding motif (KILRR). Novel peptide derivatives were modified substituting hydrophobic amino acids at positions 5 or 7, both, positively charged lysines (L5K, L7K). These tested antimicrobial activities against biofilm-forming Staphylococcus epidermidis multiple other microbes using crystal violet broth microdilution assays, respectively. To assess impact on mammalian cells, toxicity determined through hemolysis cytotoxicity assays. The stability candidate BiF2_5K7K, assessed human serum secondary structure membrane-like environments analyzed circular dichroism. action BiF2_5K7K planktonic S. effect cell viability via viable counting Its mechanism investigated confocal laser scanning microscopy transcription analysis. Additionally, ability eradicate mature biofilms examined colony counting. Finally, preliminary evaluation involved coating catheter preventive efficacy formation surrounding area. Results exhibited dose-dependent . It inhibited subinhibitory concentrations altering extracellular polysaccharide production quorum-sensing gene expression. it broad-spectrum no significant lines observed. is retained when exposed serum. In environments, this formed α-helix amphipathic structure. Within 4 h, reduction number colonies observed, demonstrating fast peptide. As test, BiF2_5K7K-coated able prevent development both surface Conclusions safety effectiveness we suggest that further developed combat infections, particularly those

Язык: Английский

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Local Delivery of Glabridin by Biomolecular Microneedle to Accelerate Infected Wound Healing

Advanced Healthcare Materials, Год журнала: 2023, Номер 13(2)

Опубликована: Окт. 11, 2023

Abstract Applying antibacterial polymers and pro‐regenerative small molecules are two individual strategies for accelerating wound healing. However, integrating those unique approaches into one therapeutic platform that meets clinical requirements is still a challenge. Herein, series of gelatin methacrylate (GelMA)/ε‐polylysine (ε‐PL) composite hydrogels (termed as GP‐n HGs, n = 0, 10, 20, 30, respectively) innovatively fabricated by ultraviolet light (UV) crosslinking. The HGs proved to be broad‐spectrum biocompatible. Among the GP‐20 HG selectively processed microneedle following mold‐casting method. Then, glabridin loaded needles produce termed GP‐20@Gla MN. An S. aureus ‐infected full‐thickness defect model in rats created evaluate wound‐healing effect Furthermore, an RNA sequencing assay performed explore possible molecular mechanisms promoting tissue regeneration, many positive routes summarized. This work significant novelty fulfilling complex needs simultaneously optimizing advanced microneedles' chemical compositions physical structures. will provide promising treating infected chronic wounds.

Язык: Английский

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