Binary Encoding of Random Peptide Sequences for Selective and Differential Antimicrobial Mechanisms

Zvi Hayouka, Angelo Bella, Tal Stern, Santanu Ray, Haibo Jiang, Chris R. M. Grovenor, Maxim G. Ryadnov

Research output: Contribution to journalArticle

Abstract

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.
Original languageEnglish
Pages (from-to)8099-8103
Number of pages5
JournalAngewandte Chemie-International Edition
Volume56
Issue number28
DOIs
Publication statusPublished - 8 Jun 2017

Keywords

  • antibiotics
  • diastereomers
  • fluorescence imaging
  • MRSA
  • protein design

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