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

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:23

Article

Hu, Xin¹  Vujanac, Milos²  Southall, Noel¹  Stebbins, C. Erec² 

[1] NIH, Chem Genom Ctr, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA

[2] Rockefeller Univ, Lab Struct Microbiol, New York, NY 10065 USA

关键词: Yersinia virulence;    YopH;    High throughput screening;    Virtual screening;   

DOI  :  10.1016/j.bmcl.2012.12.018

来源: Elsevier

【 摘 要 】

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. (C) 2012 Elsevier Ltd. All rights reserved.

【 授权许可】

Free