Peptoid-Peptide Hybrid Analogs of the Enterococcus faecalis Fsr Auto-Inducing Peptide (AIP) Reveal Crucial Structure-Activity Relationships.
Peptoid-Peptide Hybrid Analogs of the Enterococcus faecalis Fsr Auto-Inducing Peptide (AIP) Reveal Crucial Structure-Activity Relationships.
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粪肠球菌 Fsr 自诱导肽 (AIP) 的肽-肽混合类似物揭示了重要的结构-活性关系。
DOI：
10.1002/cbic.202200527
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Tal-Gan,Yftah
中科院分区：
文献类型：
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作者：
McBrayer,DominicN;Ghosh,Uttam;Lella,Muralikrishna;Cameron,CrisseyD;Tal-Gan,Yftah
随着耐多药细菌对人类健康的威胁越来越大，人们正在越来越多地研究治疗细菌感染的替代方法。粪肠球菌是一种机会性病原体，是继发性肠球菌感染的主要原因。其致病性已被证明在很大程度上依赖于称为群体感应的细胞密度通讯机制。在这项研究中，我们对使用byE的含内酯的大环信号肽进行了系统的研究。Fsr介导的通讯，被称为明胶酶生物合成激活信息素（GBAP）。具体来说，通过结合树脂亚单体和液相类肽构建块合成方法，我们成功地合成了GBAP的类肽-肽杂化类似物库，并确定了引入类肽（N -烷基甘氨酸衍生物）修饰后的生物效应。在肽的大环区域内，正如其他修饰所见，与其他大环位点相比，F7位点对类肽修饰具有异常的耐受性。有趣的是，在外环尾部，N2位点的肽类修饰完全消除了活性，这是单尾修饰的第一次。
As multidrug‐resistant bacteria become a more pressing risk to human health, alternate approaches to treating bacterial infections are being increasingly investigated.Enterococcus faecalisis an opportunistic pathogen responsible for a large percentage of secondary enterococci infections. Its pathogenicity has been shown to be largely dependent on a cell‐density communication mechanism, termed quorum sensing. In this study, we conducted a systematic investigation of the lactone‐containing macrocyclic signaling peptide used byE. faecalisfor Fsr‐mediated communication, termed gelatinase biosynthesis activating pheromone (GBAP). Specifically, through a combination of the on‐resin sub‐monomer and solution phase peptoid building block synthesis approaches, we successfully synthesized a library of peptoid‐peptide hybrid analogs of GBAP and determined the biological effects associated with the introduction of the peptoid (N‐alkyl glycine derivative) modifications. Within the macrocycle region of the peptide, as have been seen with other modifications, the F7 site was unusually tolerant toward peptoid modification, compared with other macrocyclic sites. Interestingly, within the exocyclic tail, peptoid modification at the N2 site completely abolished activity, a first for a single tail modification.