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, seve...

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Published inBioorganic & medicinal chemistry letters Vol. 13; no. 15; pp. 2449 - 2453
Main Authors Scott, R.John, Lian, Lu-Yun, Muharram, S.Hanna, Cockayne, Alan, Wood, Stewart J, Bycroft, Barrie W, Williams, Paul, Chan, Weng C
Format Journal Article
LanguageEnglish
Published Oxford Elsevier Ltd 04.08.2003
Elsevier
Subjects
4-Butyrolactone - analogs & derivatives
4-Butyrolactone - pharmacology
Antibacterial agents
Antibiotics. Antiinfectious agents. Antiparasitic agents
Bacterial Proteins - genetics
Bacteriology
Biological and medical sciences
Cyclization
Dose-Response Relationship, Drug
Drug Design
Fundamental and applied biological sciences. Psychology
Genes, Reporter - genetics
Indicators and Reagents
Lactones - antagonists & inhibitors
Medical sciences
Microbiology
Pathogenicity, virulence, toxins, bacteriocins, pyrogens, host-bacteria relations, miscellaneous strains
Peptides - antagonists & inhibitors
Pharmacology. Drug treatments
Signal Transduction - physiology
Staphylococcus - drug effects
Staphylococcus - genetics
Staphylococcus - physiology
Structure-Activity Relationship
Trans-Activators - genetics
Tyrosine
Cyclic peptides
Virulence
Staphylococcus
Pseudopeptide
Signal transduction
Structure activity relation
Bacteria
Micrococcales
Micrococcaceae
Peptide synthesis
Inhibition
Solid phase
Chemical synthesis
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Summary: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. Graphic
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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ISSN:0960-894X
1464-3405
DOI:10.1016/S0960-894X(03)00497-9