Highly Stable, Amide‐Bridged Autoinducing Peptide Analogues that Strongly Inhibit the AgrC Quorum Sensing Receptor in Staphylococcus aureus
Abstract
Blocking quorum sensing (QS) pathways has attracted considerable interest as an approach to suppress virulence in bacterial pathogens. Toward this goal, we recently developed analogues of a native autoinducing peptide (AIP‐III) signal that can inhibit AgrC‐type QS receptors and attenuate virulence phenotypes in Staphylococcus aureus. Application of these compounds is limited, however, as they contain hydrolytically unstable thioester linkages and have only low aqueous solubilities. Herein, we report amide‐linked AIP analogues with greatly enhanced hydrolytic stabilities and solubilities relative to our prior analogues, whilst maintaining strong potencies as AgrC receptor inhibitors in S. aureus. These compounds represent powerful tools for the study of QS.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jun 08, 2016
- Source ID
- 10.1002/ange.201602974
Entities
People
- Gabriel Cornilescu
- Helen Blackwell
- Monika Ivancic
- Tian Yang
- Yftah Tal-Gan
Organizations
- National Institutes of Health
- University of Nevada, Reno
- University of Vermont
- University of Wisconsin–Madison