Side-chain-to-tail thiolactone peptide inhibitors of the staphylococcal quorum-sensing system.
The expression of many staphylococcal virulence factors are regulated by the agr locus via a two-component signal transduction system (TCSTS), which is activated in response to a secreted autoinducer peptide (AIP). By exploiting the unique chemical architecture of the naturally occurring AIP-1, several potent inhibitors of staphylococcal TCSTS were designed and synthesized using either a linear or branched solid-phase approach. These inhibitors are competitive binders and contain the crucial 16-membered side-chain-to-tail thiolactone peptide pharmacophore.
Scott
R John
RJ
School of Pharmaceutical Sciences, University of Nottingham, University Park, Nottingham NG7 2RD, UK.
Lian
Lu-Yun
LY
Muharram
S Hanna
SH
Cockayne
Alan
A
Wood
Stewart J
SJ
Bycroft
Barrie W
BW
Williams
Paul
P
Chan
Weng C
WC
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics; D003500:Cyclization; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D017930:Genes, Reporter / Q000235:genetics; D007202:Indicators and Reagents; D007783:Lactones / Q000037:antagonists & inhibitors*; D010455:Peptides / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000502:physiology; D013210:Staphylococcus / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D013329:Structure-Activity Relationship; D015534:Trans-Activators / Q000235:genetics; D014443:Tyrosine
C095698:Agr protein, Staphylococcus aureus; D001426:Bacterial Proteins; D007202:Indicators and Reagents; D007783:Lactones; D010455:Peptides; D015534:Trans-Activators; D014443:Tyrosine; C030654:N-(3-oxohexanoyl)-3-aminodihydro-2(3H)-furanone; D015107:4-Butyrolactone