Potential inhibitors of S-adenosylmethionine-dependent methyltransferases. 7. Role of the ribosyl moiety in enzymatic binding of S-adenosyl-L-homocysteine and S-adenosyl-L-methionine.
A series of 2',3'-acyclic analogues of S-adenosyl-L-homocysteine were synthesized and evaluated as inhibitors of S-adenosyl-L-methionine-dependent methyltransferases. The 2',3'-acyclic analogues were prepared by periodate oxidation of the corresponding ribonucleosides, followed by reduction of the intermediate dialdehydes with sodium borohydride. These 2',3'-acyclic ribonucleosides were inactive as inhibitors of histamine N-methyltransferase, catechol O-methyltransferase, phenylethanolamine N-methyltransferase, and hydroxyindole O-methyltransferase. These results suggest that the rigidity of the ribosyl ring of S-adenosyl-L-homocysteine is crucial to its enzymatic bindings.
D000818:Animals; D002417:Cattle; D006168:Guinea Pigs; D006710:Homocysteine / Q000031:analogs & derivatives*; D066298:In Vitro Techniques; D008297:Male; D008722:Methods; D008780:Methyltransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D012435:S-Adenosylhomocysteine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology; D012436:S-Adenosylmethionine / Q000378:metabolism*; D013329:Structure-Activity Relationship
D006710:Homocysteine; D012436:S-Adenosylmethionine; D012435:S-Adenosylhomocysteine; D008780:Methyltransferases