Premium
Binary Encoding of Random Peptide Sequences for Selective and Differential Antimicrobial Mechanisms
Author(s) -
Hayouka Zvi,
Bella Angelo,
Stern Tal,
Ray Santanu,
Jiang Haibo,
Grovenor Chris R. M.,
Ryadnov Maxim G.
Publication year - 2017
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201702313
Subject(s) - antimicrobial , peptide , chirality (physics) , staphylococcus aureus , sequence (biology) , amino acid , chemistry , peptide sequence , bacteria , encoding (memory) , biology , computational biology , combinatorial chemistry , microbiology and biotechnology , biochemistry , genetics , gene , physics , quantum mechanics , nambu–jona lasinio model , quark , neuroscience , chiral symmetry breaking
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.