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

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Abstract
A series of 2'',3''-acyclic analogs of S-adenosyl-L-homocysteine were synthesized and evaluated as inhibitors of S-adenosyl-L-methionine-dependent methyltransferases [rat liver, bovine adrenal medulla and pineal gland and guinea pig brain]. The 2'',3''-acyclic analogs were prepared by periodate oxidation of the corresponding ribonucleosides, followed by reduction of the intermediate dialdehydes with NaBH4. These 2'',3''-acyclic ribonucleosides were inactive as inhibitors of histamine N-methyltransferase, catechol 0-methyltransferase, phenylethanolamine N-methyltransferase, and hydroxyindole 0-methyltransferase. These results suggest that the rigidity of the ribosyl ring of S-adenosyl-L-homocysteine is crucial to its enzymatic binding.