Synthesis and bioassay of a protein tyrosine phosphatase inhibitor, dephostatin

✍ Scribed by Libing Yu; Andrea McGill; Johnny Ramirez; Peng George Wang; Zhong-Yin Zhang

• Publisher: Elsevier Science
• Year: 1995
• Tongue: English
• Weight: 167 KB
• Volume: 5
• Category: Article
• ISSN: 0960-894X
• DOI: 10.1016/0960-894x(95)00156-n

✦ Synopsis

The synthesis of natural product, dephostatin, is described. Both dephostatin and N-methyl-Nnitrosoaniline are found to inactivate the homogeneous recombinant Yersinia and mammalian protein tyrosine phosphatases in a concentration and lime dependent manner.

The tyrosine phosphorylation on target protein is tightly controlled by the concerted actions of both protein tyrosine kinases and protein tyrosine phosphatases (PTP; EC 2.7.1.112).1 While much information exists regarding protein tyrosine kinase inhibitors, there has been little progress in the identification and design of PTP inhibitors. 2 Dephostatin 1, a PTP inhibitor, was recently isolated from the culture broth of streptomyces sp. 3 We have been investigating the mechanism of the inhibition by dephostatin since it contains a unique N-nitrosamine functionality. Here we report the synthesis and bioassay of 1 and its unsubstituted precursor, N-methyl-Nnitrosoaniline 2.