Development of molecular probes for second-site screening and design of protein tyrosine phosphatase inhibitors.

Basic Information

ID: ALA1147128

Journal: J Med Chem

Title: Development of molecular probes for second-site screening and design of protein tyrosine phosphatase inhibitors.

Authors: Vazquez J, Tautz L, Ryan JJ, Vuori K, Mustelin T, Pellecchia M.

Abstract: We report on the design, synthesis, and evaluation of a series of furanyl-salicyl-nitroxide derivatives as effective chemical probes for second-site screening against phosphotyrosine phosphatases (PTPs) using NMR-based techniques. The compounds have been tested against a panel of PTPs to assess their ability to inhibit a broad spectrum of these phosphatases. The utility of the derived compounds is illustrated with the phosphatase YopH, a bacterial toxin from Yersinia pestis. Novel chemical fragments were identified during an NMR-based screen for compounds that are capable of binding on the surface of YopH in regions adjacent the catalytic site in the presence of the spin-labeled compounds. Our data demonstrate the value of the derived chemical probes for NMR-based second-site screening in PTPs.

CiteXplore: 17394300

DOI: 10.1021/jm061481l

Patent ID: