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.