Adenosine-5'-carboxaldehyde: a potent inhibitor of S-adenosyl-L-homocysteine hydrolase.
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.
Liu
S
S
Department of Medicinal Chemistry, University of Kansas, Lawrence 66045.
Wnuk
S F
SF
Yuan
C
C
Robins
M J
MJ
Borchardt
R T
RT
D000241:Adenosine / Q000031:analogs & derivatives*; D043383:Adenosylhomocysteinase; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003839:Deoxyadenosines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006867:Hydrolases / Q000037:antagonists & inhibitors*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D013329:Structure-Activity Relationship
D003839:Deoxyadenosines; D004791:Enzyme Inhibitors; C080528:adenosine-5'-carboxaldehyde; D006867:Hydrolases; D043383:Adenosylhomocysteinase; D000241:Adenosine