期刊
SMALL
卷 17, 期 7, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/smll.202003899
关键词
cross-strand interaction; immunomodulatory; in vivo efficacy; beta-hairpin antimicrobial peptide; beta-turn
类别
资金
- National Natural Science Foundation of China [32030101, 31872368, 31672434]
- China Agriculture Research System [CARS-35]
- Natural Science Foundation of Heilongjiang Province [TD2019C001]
Novel antimicrobial peptides have been developed as potential antibiotic substitutes, with a focus on a progressive beta-hairpin solution to reveal the balance between function and toxicity of structural moieties. Lead amphiphiles have shown promising antimicrobial efficacy and potential inflammation-limiting capabilities without observed toxicity, providing renewed innovation in beta-sheet peptide-based antimicrobial biomaterials.
Novel antimicrobial peptides (AMPs) have revolutionarily evolved into formidable candidates for antibiotic substitute materials against pathogenic infections. However, cost, lability, disorderly sequences, systemic toxicology, and biological profiles have plagued the perennial search. Here, a progressive beta-hairpin solution with the simplest formulation is implanted into an AMP-based therapeutic strategy to systematically reveal the complex balance between function and toxicity of structural moieties, including cationicity, hydrophobicity, cross-strand interactions, center bending, and sequence pattern. Comprehensive implementation of structural identification, ten microorganisms, eleven in vitro barriers, four mammalian cells, and a diversified membrane operation setup led to the emergence of beta-hairpin prototypes from a 24-member library. Lead amphiphiles, WKF-PG and WRF-NG, can tackle bacterial infection through direct antimicrobial efficacy and potential inflammation-limiting capabilities, such as an Escherichia coli challenge in a mouse peritonitis-sepsis model, without observed toxicity after systemic administration. Their optimal states with dissimilar modulators and the unavailable drug resistance related to membrane lytic mechanisms, also provide an usher for renewed innovation among beta-sheet peptide-based antimicrobial biomaterials.
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