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Design, Synthesis and Evaluation of AdSS Bisubstrate Inhibitors
Author(s) -
Tibrewal Nidhi,
Elliott Gregory I.
Publication year - 2020
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.202000498
Subject(s) - purine nucleoside phosphorylase , moiety , linker , nucleic acid , chemistry , biochemistry , nucleoside , purine , enzyme , adenosine , stereochemistry , combinatorial chemistry , purine metabolism , adenosine deaminase , computer science , operating system
Many cancers lack the expression of methylthioadenosine phosphorylase (MTAP). These cancers require adenylosuccinate synthetase (AdSS) for nucleic acid synthesis. By inhibiting adenylosuccinate synthetase, we potentially have a new therapeutic agent. Bisubstrate inhibitors were synthesized and evaluated against purified AdSS. The best activity was obtained with adenosine bearing a four‐carbon linker that connects the N ‐formyl‐ N ‐hydroxy moiety to the 6‐position of the purine nucleoside.