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

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.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

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

doi

10.1021/jm061481l

subject

Has Abstract

pub_date

2007-05-03 00:00:00

pages

2137-43

issue

9

eissn

0022-2623

issn

1520-4804

journal_volume

50

pub_type

杂志文章

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