Combating drug-resistant bacteria with sulfonium cationic poly(methionine)

Abstract antibiotic resistance and drug-resistant bacterial infections pose significant threats to public health. Antimicrobial peptides (AMPs) are a promising candidate for related-infection therapy, but their clinical application is limited by their high synthesis cost and susceptibility to protea...

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Bibliographic Details
Published in:RSC advances 2023-09, Vol.13 (39), p.2768-27612
Main Authors: Zhu, Lizhong, Li, Jie, Huan, Weiwei
Format: Article
Language:English
Subjects:
Alkylation
Amino acids
Antibiotics
Bacteria
Biocompatibility
Cations
Chemistry
Lysine
Methionine
Peptides
Public health
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Summary:Abstract antibiotic resistance and drug-resistant bacterial infections pose significant threats to public health. Antimicrobial peptides (AMPs) are a promising candidate for related-infection therapy, but their clinical application is limited by their high synthesis cost and susceptibility to protease degradation. To address these issues, cationic poly(α-amino acid)s based on lysine have been developed as synthetic mimics of AMPs. In this study, we introduce a new class of cationic AMP synthetic mimics based on functional poly(methionine)s. We synthesized a series of sulfonium cationic poly( d , l -methionine)s with varying chain lengths via a convenient polymerization on α-amino acid thiocarboxyanhydride (α-NTA) using tert-butyl-benzylamine as the initiator, followed by alkylation with iodomethane. Our optimal methionine polymer demonstrated potent and broad-spectrum antibacterial activity against antibiotic-resistant bacteria, as well as excellent biocompatibility with mammalian cells and rapid bactericidal performance. Our findings suggest that sulfonium poly(methionine)s have the potential to address the challenge of drug-resistant bacterial infections. The sulfonium poly-methionine displays antibacterial activity against antibiotic-resistant bacteria and excellent biocompatibility with mammalian cell, indicating the huge potential in addressing the challenge of drug-resistant bacterial infections.
ISSN:2046-2069
2046-2069
DOI:10.1039/d3ra03925k