Adenosine-5'-carboxaldehyde: a potent inhibitor of S-adenosyl-L-homocysteine hydrolase

Abstract

Adenosine-5'-carboxaldehyde (3) and its 4'-epimer (4) were synthesized and shown to be potent type I mechanism-based inhibitors of recombinant rat liver AdoHcy hydrolase with k2/KI values of 16.7 x 10(-3) and 5.5 x 10(-3) nM-1 min-1, respectively. The observation that 3 and 4 are potent inhibitors of AdoHcy hydrolase supports the hypothesis that they function as key intermediates in the mechanism by which the (Z)- and (E)-4',5'-didehydro-5'-deoxy-5'-fluoroadenosines 1 and 2 inactivate this enzyme.