RATIONALLY DESIGNED INHIBITORS OF INOSINE MONOPHOSPHATE DEHYDROGENASE

Functionalized 2-alkyl derivatives of inosinic acid have been synthesi zed to serve as reversible as well as irreversible inhibitors of the h uman type II enzyme inosine monophosphate dehydrogenase. These compoun ds were designed to react with Cys-331 of the enzyme to form covalent bonds so as to interfere with the normal enzyme mechanism which involv es attack of Cys-331 at C-2 of the substrate. Mass spectrometric analy sis of the reaction products after enzymatic degradation confirmed the appropriateness of the inhibitor design.