Novel β-hairpin amphiphiles utilizing tryptophan-interacting propensities exhibit multimodal antibacterial mechanism and promote wound healing in drug-resistant infections

作者：Mengcheng Wang, Hongrui Guan, Jianan Pang, Yuanmengxue Wang, Baojing Cheng, Yongjie Zhu, Na Dong, A. S. Shan, Changxuan Shao · 发表于：Journal of Advanced Research · 年份：2026 · DOI：10.1016/j.jare.2026.06.031 · 被引用次数：1 · 研究领域：Antimicrobial agents and applications、Antimicrobial Peptides and Activities、Supramolecular Self-Assembly in Materials

INTRODUCTION: The emergence of multidrug-resistant bacteria constitutes a severe global health threat that requires effective countermeasures. In this context, antimicrobial peptides (AMPs) represent promising candidates for the development of new antibiotics. OBJECTIVES: In this study, the unique structural properties of tryptophan were leveraged to develop novel β-hairpin amphiphiles. Specifically, via tryptophan-mediated interstrand π-π and CH-π interactions, the β-hairpin conformation was stabilized without resorting to traditional disulfide bonds, thereby enabling the construction of the simplest β-sheet scaffold. METHODS: Peptides were synthesized via the Fmoc solid-phase method, and their secondary structures were determined by circular dichroism spectroscopy. In vitro experiments included the determination of minimum inhibitory concentration (MIC), evaluations of stability (salts, serum, and extreme pH), and assessments of toxicity (cytotoxicity and hemolysis). Mechanisms of action were explored by measuring inner and outer membrane permeability, combined with fluorescence microscopy, electron microscopy, flow cytometry, assays for respiratory chain dehydrogenase activity, adenosine triphosphate (ATP) alteration, and reactive oxygen species (ROS) generation, as well as transcriptomic analysis. In vivo efficacy was validated in mouse models of Escherichia coli-induced peritonitis-sepsis and methicillin-resistant Staphylococcus aureus (MRSA)-infected skin wounds. RESULT...