Binary Encoding of Random Peptide Sequences for Selective and Differential Antimicrobial Mechanisms
Binary Encoding of Random Peptide Sequences for Selective and Differential Antimicrobial Mechanisms
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DOI：
10.1002/anie.201702313
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发表时间：
2017-07-03
影响因子：
16.6
通讯作者：
Ryadnov, Maxim G.
中科院分区：
文献类型：
--
作者：
Hayouka, Zvi;Bella, Angelo;Ryadnov, Maxim G.
二进制编码的肽序列的差异抗菌机制的报告。这种序列在组成上是随机的，但在链长上是可控的，由相同的两个氨基酸组装而成，但其中一个氨基酸的立体化学不同。不管手性如何，这些序列裂解细菌，包括“超级细菌”耐甲氧西林金黄色葡萄球菌（MRSA）和耐万古霉素肠球菌（VRE）。具有相同手性的序列，即所谓的纯手性序列，组装成抗菌孔并形成生物学上混杂和溶血的连续螺旋。相比之下，缺乏这种持久性的异手性序列选择性地攻击细菌膜而不寡聚成可见的孔。这些结果为设计膜选择性和序列独立性抗菌剂提供了机理依据。
Binary encoding of peptide sequences into differential antimicrobial mechanisms is reported. Such sequences are random in composition, but controllable in chain length, are assembled from the same two amino acids, but differ in the stereochemistry of one. Regardless of chirality, the sequences lyse bacteria including the "superbugs" methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE). Sequences with the same chirality, so-called homochiral sequences, assemble into antimicrobial pores and form contiguous helices that are biologically promiscuous and hemolytic. By contrast, heterochiral sequences that lack such persistence selectively attack bacterial membranes without oligomerizing into visible pores. These results offer a mechanistic rationale for designing membrane-selective and sequence-independent antimicrobials.