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.
Guillerm
Georges
G
Laboratoire de Chimie bioorganique, UMR 6519, UFR Sciences, B.P. 1039, 51687 Reims Cedex 2, France.
Muzard
Murielle
M
Glapski
Cédric
C
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D043383:Adenosylhomocysteinase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002264:Carboxylic Acids / Q000737:chemistry* / Q000494:pharmacology; D004952:Esters; D006801:Humans; D011480:Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology
D002264:Carboxylic Acids; D004952:Esters; D011480:Protease Inhibitors; D043383:Adenosylhomocysteinase; D000241:Adenosine