Positive Charge-Concentrated Dimeric Lipopeptides with Enhanced Protease Resistance: A Potential Solution for Systemic Bacterial Infections

Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Antimicrobial peptides (AMPs) show potential as antibiotic alternatives for bacterial infections; nevertheless, the susceptibility to proteases limits their broader utilization. This study developed engineered lipopeptides using antienzymolysis modifications and cysteine (Cys)-dimerization strategy. As key parameters functioning of AMPs, hydrophobicity positive charges were concentrated within peptide sequence by adjusting intermolecular disulfide bond placement distribution effects. Their centralization in induces a differential propensity toward membranes. Positive charge-concentrated dimeric lipopeptide (C-C

Language: Английский

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Advancements in peptide-based antimicrobials: A possible option for emerging drug-resistant infections

Advances in Colloid and Interface Science, Journal Year: 2024, Volume and Issue: 333, P. 103282 - 103282

Published: Sept. 6, 2024

Language: Английский

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Serum-Stable, Cationic, α-Helical AMPs to Combat Infections of ESKAPE Pathogens and C. albicans

ACS Applied Bio Materials, Journal Year: 2025, Volume and Issue: unknown

Published: April 30, 2025

Expedition in the rate of development antimicrobial resistance accompanied by slowdown new antimicrobials has led to a dire necessity develop an alternate class agents. Antimicrobial peptides (AMPs), available nature, are effective molecules that can combat microbial infections. However, due several inherent shortcomings such as salt sensitivity their potency, short systemic half-lives owing protease and serum degradation, cytotoxicity, commercial success is limited. Inspired α helical AMPs present here this work, we have developed two short, cationic, RR-12 FL-13. Both exhibited high broad-spectrum activity, tolerance, prompt bactericidal considerable stability, remaining non-cytotoxic non-hemolytic at relevant microbicidal concentrations. The designed were membranolytic toward strains, though there subtle differences mechanism variation composition cell membranes different microbes. Rigorous experimental techniques molecular dynamics (MD) simulations performed understand structure, mechanisms detail. Positive charge, balanced hydrophobicity-hydrophilicity, conformation attributes superior performance AMPs, making them valuable additions repertoire therapeutically promising antimicrobials.

Language: Английский

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An Overview of Frog Skin-Derived Esc Peptides: Promising Multifunctional Weapons against Pseudomonas aeruginosa-Induced Pulmonary and Ocular Surface Infections

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(8), P. 4400 - 4400

Published: April 16, 2024

Antimicrobial resistance is a silent pandemic harming human health, and Pseudomonas aeruginosa the most common bacterium responsible for chronic pulmonary eye infections. peptides (AMPs) represent promising alternatives to conventional antibiotics. In this review, in vitro/in vivo activities of frog skin-derived AMP Esc(1-21) are shown. rapidly kills both planktonic sessile forms P. stimulates migration epithelial cells, likely favoring repair damaged tissue. However, undertake preclinical studies, some drawbacks AMPs (cytotoxicity, poor biostability, limited delivery target site) must be overcome. For purpose, stereochemistry two amino acids was changed obtain diastereomer Esc(1-21)-1c, which more stable, less cytotoxic, efficient treating aeruginosa-induced lung cornea infections mouse models. Incorporation these (Esc peptides) into nanoparticles or immobilization medical device (contact lens) revealed an effective strategy ameliorate and/or prolong peptides’ antimicrobial efficacy. Overall, data make Esc encouraging candidates novel multifunctional drugs treat pathology especially patients with cystic fibrosis dysfunctions, characterized by tissue injury bacterial infection.

Language: Английский

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A Nonfouling Electrochemical Biosensor for Protein Analysis in Complex Body Fluids Based on Multifunctional Peptide Conjugated with PEGlyated Phospholipid

ACS Sensors, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 17, 2024

Developing antifouling biosensors capable of performing robustly in complex human body fluids is crucial for biomarker diagnosis and health monitoring. Herein, an highly sensitive stable biosensor was constructed through the self-assembly designed conjugates composed a multifunctional peptide (MP) PEGylated distearoylphosphatidylethanolamine (DSPE-PEG). The capability DSPE-PEG-MP demonstrated clearly coarse-grained molecular dynamics simulation transmission electron microscopy, it can be effectively self-assembled onto electrode surface modified with gold nanoparticles. MP to contained sequence that specifically bind target protein Annexin A1 (ANXA1), D-type amino acid composition enhance its resistance enzymatic hydrolysis. unique design MP, conjugation phospholipid DSPE-PEG, enabled exhibit excellent stability various fluids. sensitively selectively quantifying ANXA1 achieved limit detection down 0.12 pg mL

Language: Английский

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