Disulfide-bonded YC18: A membrane-targeting peptide with superior efficacy against Staphylococcus aureus infections

	Disulfide-bonded YC18: A membrane-targeting peptide with superior efficacy against Staphylococcus aureus infections
	Gao, JN; Wang, Y; Wang, WT; Yang, M; Cao, KX; Pan, Q; Guo, RY; Lu, QM; Zhang, CC; Li, J; Lai, R
	2026
发表期刊	Bioorganic Chem.
ISSN	0045-2068
卷号	168
摘要	The escalating crisis of antimicrobial resistance, particularly in Staphylococcus aureus (S. aureus) infections, demands innovative therapeutics beyond conventional antibiotics. Spider venom represents a rich source of bioactive peptides with untapped therapeutic potential. Here, we report YC18, a novel disulfide-stabilized beta-hairpin peptide derived from the cDNA library of Chilobrachys liboensis (C. liboensis). This peptide exhibits potent and selective activity against S. aureus, with a minimum inhibitory concentration (MIC) of 6.25 mu g/mL. Unlike vancomycin, YC18 exhibits low resistance development even after 35 serial passages of S. aureus, underscoring its clinical potential. Structural prediction revealed that YC18's unique dual-disulfide scaffold (Cys2-Cys15, Cys6-Cys11) confers exceptional stability and efficacy, as validated by peptide analog studies. Mechanistically, YC18 selectively targets phosphatidylglycerol (PG) to disrupt bacterial membranes, a process elucidated through molecular dynamics simulations. With high plasma stability, low cytotoxicity, and efficacy in murine infection models, YC18 emerges as a promising candidate for combating S. aureus infections.
收录类别	SCIE
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/14835
专题	科研部门_天然药物功能蛋白质学科组（赖仞）
推荐引用方式 GB/T 7714	Gao, JN,Wang, Y,Wang, WT,et al. Disulfide-bonded YC18: A membrane-targeting peptide with superior efficacy against Staphylococcus aureus infections[J]. Bioorganic Chem.,2026,168.
APA	Gao, JN.,Wang, Y.,Wang, WT.,Yang, M.,Cao, KX.,...&Lai, R.(2026).Disulfide-bonded YC18: A membrane-targeting peptide with superior efficacy against Staphylococcus aureus infections.Bioorganic Chem.,168.
MLA	Gao, JN,et al."Disulfide-bonded YC18: A membrane-targeting peptide with superior efficacy against Staphylococcus aureus infections".Bioorganic Chem. 168(2026).

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