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Simplified AIP‐II Peptidomimetics Are Potent Inhibitors of Staphylococcus aureus AgrC Quorum Sensing Receptors
Author(s) -
Vasquez Joseph K.,
TalGan Yftah,
Cornilescu Gabriel,
Tyler Kimberly A.,
Blackwell Helen E.
Publication year - 2017
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201600516
Subject(s) - peptidomimetic , quorum sensing , peptide , staphylococcus aureus , chemistry , virulence , biochemistry , molecular mimicry , receptor , microbiology and biotechnology , stereochemistry , combinatorial chemistry , biology , bacteria , gene , genetics , antigen
Abstract The bacterial pathogen Staphylococcus aureus controls many aspects of virulence by using the accessory gene regulator (agr) quorum sensing (QS) system. The agr system is activated by a macrocyclic peptide signal known as an autoinducing peptide (AIP). We sought to develop structurally simplified mimetics of AIPs for use as chemical tools to study QS in S. aureus . Herein, we report new peptidomimetic AgrC receptor inhibitors based on a tail‐truncated AIP‐II peptide that have almost analogous inhibitory activities to the parent peptide. Structural comparison of one of these peptidomimetics to the parent peptide and a highly potent, all‐peptide‐derived, S. aureus agr inhibitor (AIP‐III D4A) revealed a conserved hydrophobic motif and overall amphipathic nature. Our results suggest that the AIP scaffold is amenable to structural mimicry and minimization for the development of synthetic agr inhibitors.