Inhibitors of inosine monophosphate dehydrogenase: probes for antiviral drug discovery.
The role of inosine monophosphate dehydrogenase (IMPDH) at the metabolic branch point of de novo purine nucleotide biosynthesis makes this enzyme an attractive probe for the discovery of antiviral compounds. Introduction of unsaturation at the 2-position of IMP, the natural substrate for IMPDH, produces Michael acceptors at that position, which results in these compounds being inhibitors of IMPDH. Consistent with this mechanism-based molecular design, some of the parent nucleosides exhibited antiviral activity.
Story
Sherry
S
Department of Pharmaceutical and Biomedical Sciences, The University of Georgia, Athens, Georgia, 30602, USA.
Gupta
Mukta
M
Bonsu
Eric
E
Nair
Vasu
V
D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors*; D007700:Kinetics; D008956:Models, Chemical; D008958:Models, Molecular; D013379:Substrate Specificity
D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D007168:IMP Dehydrogenase