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Bioorg Med Chem Lett. 2013 Feb 15;23(4):1056-62. doi: 10.1016/j.bmcl.2012.12.018. Epub 2012 Dec 20.

Inhibitors of the Yersinia protein tyrosine phosphatase through high throughput and virtual screening approaches.

Author information

1
NIH Chemical Genomics Center, National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Rockville, MD 20850, USA.

Abstract

The bacterial protein tyrosine phosphatase YopH is an essential virulence determinant in Yersinia pestis and a potential antibacterial drug target. Here we report our studies of screening for small molecule inhibitors of YopH using both high throughput and in silico approaches. The identified inhibitors represent a diversity of chemotypes and novel pTyr mimetics, providing a starting point for further development and fragment-based design of multi-site binding inhibitors. We demonstrate that the applications of high throughput and virtual screening, when guided by structural binding mode analysis, is an effective approach for identifying potent and selective inhibitors of YopH and other protein phosphatases for rational drug design.

PMID:
23294700
PMCID:
PMC3563096
DOI:
10.1016/j.bmcl.2012.12.018
[Indexed for MEDLINE]
Free PMC Article

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