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Potential inhibitors of S-adenosylmethionine-dependent methyltransferases. 6. Structural modifications of S-adenosylmethionine. 1976

R T Borchardt, and Y Shiong, and J A Huber, and A F Wycpalek

Structural analogues of S-adenosyl-L-methionine (SAM), with modifications in the amino acid, sugar, or base portions of the molecule, have been synthesized and evaluated as either inhibitors and/or substrates for the enzymes catechol O-methyltransferase, phenylethanolamine N-methyltransferase, histamine N-methyltransferase, and hydroxyindole O-methyltransferase. To evaluate these analogues as substrates for SAM-dependent methyltransferases, the corresponding methyl-14C compounds were prepared and tested for their abilities to donate their methyl group to the appropriate acceptor molecules. In addition, the unlabeled SAM analogues were tested for their inhibitory activities in these same transmethylation reactions. In general, it could be conlcuded from these studies that methyltransferases show very strict specificity for the structural features of SAM. This strict specificity holds for the enzymatic binding and methyl-donating abilities of this molecule. In fact, it could be concluded from the results of this study that methyltransferases show a higher specificity for the structural features of the substrate L-SAM than for the structural features of the product S-adenosyl-L-homocysteine (L-SAH).

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008297 Male Males
D008780 Methyltransferases A subclass of enzymes of the transferase class that catalyze the transfer of a methyl group from one compound to another. (Dorland, 28th ed) EC 2.1.1. Methyltransferase
D002417 Cattle Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor. Beef Cow,Bos grunniens,Bos indicus,Bos indicus Cattle,Bos taurus,Cow,Cow, Domestic,Dairy Cow,Holstein Cow,Indicine Cattle,Taurine Cattle,Taurus Cattle,Yak,Zebu,Beef Cows,Bos indicus Cattles,Cattle, Bos indicus,Cattle, Indicine,Cattle, Taurine,Cattle, Taurus,Cattles, Bos indicus,Cattles, Indicine,Cattles, Taurine,Cattles, Taurus,Cow, Beef,Cow, Dairy,Cow, Holstein,Cows,Dairy Cows,Domestic Cow,Domestic Cows,Indicine Cattles,Taurine Cattles,Taurus Cattles,Yaks,Zebus
D006168 Guinea Pigs A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001665 Binding Sites The parts of a macromolecule that directly participate in its specific combination with another molecule. Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining
D012435 S-Adenosylhomocysteine 5'-S-(3-Amino-3-carboxypropyl)-5'-thioadenosine. Formed from S-adenosylmethionine after transmethylation reactions. S Adenosylhomocysteine,Adenosylhomocysteine, S
D012436 S-Adenosylmethionine Physiologic methyl radical donor involved in enzymatic transmethylation reactions and present in all living organisms. It possesses anti-inflammatory activity and has been used in treatment of chronic liver disease. (From Merck, 11th ed) AdoMet,Ademetionine,FO-1561,Gumbaral,S Amet,S-Adenosyl-L-Methionine,S-Adenosylmethionine Sulfate Tosylate,SAM-e,Samyr,FO 1561,FO1561,S Adenosyl L Methionine,S Adenosylmethionine,S Adenosylmethionine Sulfate Tosylate
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships

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