Inactivation of S-adenosyl-L-homocysteine hydrolase by 6'-cyano-5',6'-didehydro-6'-deoxyhomoadenosine and 6'-chloro-6'-cyano-5',6'-didehydro-6'-deoxyhomoadenosine. Antiviral and cytotoxic effects.
6'-Cyano-5',6'-didehydro-6'-deoxyhomoadenosine (E)-1, (Z)-1, and 6'-chloro-6'-cyano-5',6'-didehydro-6'-deoxyhomoadenosine (E)-2 were synthesized and tested as new mechanism-based inhibitors of AdoHcy hydrolase. Nucleoside (E)-1 was identified as a type I inhibitor of the enzyme, whereas inactivation of the enzyme by nucleosides (Z)-1 and (E)-2 was accompanied by the formation of a covalent labeling of AdoHcy hydrolase.
Guillerm
Georges
G
Muzard
Murielle
M
Glapski
Cédric
C
Pilard
Serge
S
De Clercq
Erik
E
D043383:Adenosylhomocysteinase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000187:drug effects; D003839:Deoxyadenosines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014645:Herpesvirus 3, Human / Q000187:drug effects; D006801:Humans; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
C509262:6'-chloro-6'-cyano-5',6'-didehydro-6'-deoxyhomoadenosine; C509261:6'-cyano-5',6'-didehydro-6'-deoxyhomoadenosine; D000970:Antineoplastic Agents; D000998:Antiviral Agents; D003839:Deoxyadenosines; D009705:Nucleosides; D043383:Adenosylhomocysteinase