Vinyl sulfones: inhibitors of SrtA, a transpeptidase required for cell wall protein anchoring and virulence in Staphylococcus aureus.
Several small molecule vinyl sulfones were found to exhibit irreversible time-dependent inhibition of the Staphylococcus aureus sortase SrtA in vitro. A representative of these compounds was shown to impair the ability of S. aureus bacteria to bind fibronectin-coated surfaces through in vivo inhibition of SrtA-mediated linkage of fibronectin to the cell surface. These data highlight the potential use of small molecule vinyl sulfones as chemotherapeutics to prevent adhesion to and colonization of host tissues during S. aureus infection.
Frankel
Brenda A
BA
Johnson Research Foundation and the Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6059, USA.
Bentley
Matthew
M
Kruger
Ryan G
RG
McCafferty
Dewey G
DG
D019881:Aminoacyltransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001426:Bacterial Proteins; D002473:Cell Wall / Q000201:enzymology / Q000502:physiology; D003546:Cysteine Endopeptidases; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000201:enzymology* / Q000472:pathogenicity; D013450:Sulfones / Q000737:chemistry* / Q000494:pharmacology*; D014774:Virulence
D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D013450:Sulfones; C009873:divinyl sulfone; D019881:Aminoacyltransferases; C120542:sortase A; D003546:Cysteine Endopeptidases