Rationally designed inhibitors of inosine monophosphate dehydrogenase.
Functionalized 2-alkyl derivatives of inosinic acid have been synthesized to serve as reversible as well as irreversible inhibitors of the human type II enzyme inosine monophosphate dehydrogenase. These compounds were designed to react with Cys-331 of the enzyme to form covalent bonds so as to interfere with the normal enzyme mechanism which involves attack of Cys-331 at C-2 of the substrate. Mass spectrometric analysis of the reaction products after enzymatic degradation confirmed the appropriateness of the inhibitor design.
Zhang
H Z
HZ
Department of Chemistry, University of Chicago, Illinois 60637, USA.
Rao
K
K
Carr
S F
SF
Papp
E
E
Straub
K
K
Wu
J C
JC
Fried
J
J
D002851:Chromatography, High Pressure Liquid; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis*; D006801:Humans; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors*; D013058:Mass Spectrometry; D009243:NAD / Q000378:metabolism
D004791:Enzyme Inhibitors; D009243:NAD; D007168:IMP Dehydrogenase