Inhibition of the Staphylococcus aureus sortase transpeptidase SrtA by phosphinic peptidomimetics.

Published

Journal Article

During pathogenesis, Gram-positive bacteria utilize surface protein virulence factors such as the MSCRAMMs (microbial surface components recognizing adhesive matrix molecules) to aid the initiation and propagation of infection through adherence to host endothelial tissue and immune system evasion. These virulence-associated proteins generally contain a C-terminal LPXTG motif that becomes covalently anchored to the peptidoglycan biosynthesis intermediate lipid II. In Staphylococcus aureus, deletion of the sortase isoform SrtA results in marked reduction in virulence and infection potential, making it an important antivirulence target. Here we describe the chemical synthesis and kinetic characterization of a nonhydrolyzable phosphinic peptidomimetic inhibitor of SrtA derived from the LPXTG substrate sequence.

Full Text

Duke Authors

Cited Authors

  • Kruger, RG; Barkallah, S; Frankel, BA; McCafferty, DG

Published Date

  • July 1, 2004

Published In

Volume / Issue

  • 12 / 13

Start / End Page

  • 3723 - 3729

PubMed ID

  • 15186858

Pubmed Central ID

  • 15186858

Electronic International Standard Serial Number (EISSN)

  • 1464-3391

International Standard Serial Number (ISSN)

  • 0968-0896

Digital Object Identifier (DOI)

  • 10.1016/j.bmc.2004.03.066

Language

  • eng