1. Design, Synthesis and Evaluation of AdSS Bisubstrate Inhibitors.
- Author
-
Tibrewal N and Elliott GI
- Subjects
- Enzyme Inhibitors chemical synthesis, Enzyme Inhibitors chemistry, Humans, Molecular Structure, Purine Nucleosides chemical synthesis, Purine Nucleosides chemistry, Purine-Nucleoside Phosphorylase, Drug Design, Enzyme Inhibitors pharmacology, Purine Nucleosides pharmacology
- Abstract
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., (© 2020 Wiley-VCH GmbH.)
- Published
- 2020
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