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硫代二肽通过 S→N 酰基转移重排生成同源自诱导肽。

Rearrangement of Thiodepsipeptides by S → N Acyl Shift Delivers Homodetic Autoinducing Peptides.

机构信息

Center for Biopharmaceuticals and Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.

Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Stigbøjlen 4, DK-1870 Frederiksberg C, Denmark.

出版信息

J Am Chem Soc. 2021 Jul 21;143(28):10514-10518. doi: 10.1021/jacs.1c02614. Epub 2021 Jul 6.

DOI:10.1021/jacs.1c02614
PMID:34228933
Abstract

Group behavior in many bacteria relies on chemically induced communication called quorum sensing (QS), which plays important roles in the regulation of colonization, biofilm formation, and virulence. In Gram-positive bacteria, QS is often mediated by cyclic ribosomally synthesized and posttranslationally modified peptides (RiPPs). In staphylococci, for example, most of these so-called autoinducing peptides (AIPs) contain a conserved thiolactone functionality, which has also been predicted to constitute a structural feature of AIPs from other genera. Here, we show that pentameric AIPs from , , and that were previously presumed to be thiolactone-containing structures readily rearrange to become homodetic cyclopeptides. This finding has implications for the developing understanding of cross-species and potential cross-genus communication of bacteria and may help guide the discovery of peptide ligands to perturb their function.

摘要

许多细菌的群体行为依赖于化学诱导的通讯,称为群体感应 (QS),它在定植、生物膜形成和毒力的调节中起着重要作用。在革兰氏阳性菌中,QS 通常由循环核糖体合成和翻译后修饰的肽 (RiPPs) 介导。例如,在葡萄球菌中,大多数所谓的自诱导肽 (AIP) 含有保守的硫内酯官能团,这也被预测为来自其他属的 AIP 的结构特征。在这里,我们表明,以前被认为含有硫内酯结构的 、 和 的五聚体 AIP 很容易重新排列成同源二肽环。这一发现对正在发展的关于细菌跨物种和潜在跨属通讯的理解具有重要意义,并可能有助于指导发现肽配体来干扰它们的功能。

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