Inactivation of S-adenosylhomocysteine hydrolase with haloethyl and dihalocyclopropyl esters derived from homoadenosine-6'-carboxylic acid.

In a search for new inhibitors that exploit 5'-6' 'hydrolytic activity' of AdoHcy hydrolase, a new series of haloethyl and dihalocyclopropyl esters 2-3 were designed and their interaction with the enzyme studied. Incubation of the enzyme with 2-3 resulted in time- and concentration-dependent inactivation of AdoHcy hydrolase as well as almost total depletion of its NAD(+) content. Further results indicated that the 'oxidative' but not the 'hydrolytic' activity was involved in the inactivation process.