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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenosine / analogs & derivatives*
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Adenosylhomocysteinase
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Animals
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Chromatography, High Pressure Liquid
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Deoxyadenosines / chemical synthesis*
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Deoxyadenosines / chemistry
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Deoxyadenosines / pharmacology
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / pharmacology
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Hydrolases / antagonists & inhibitors*
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Liver / drug effects
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Liver / enzymology
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Rats
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Structure-Activity Relationship
Substances
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Deoxyadenosines
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Enzyme Inhibitors
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adenosine-5'-carboxaldehyde
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Hydrolases
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Adenosylhomocysteinase
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Adenosine