Synthesis and biochemical properties of chemically stable product analogues of the reaction catalyzed by S-adenosyl-L-methionine decarboxylase.
Structural analogues of decarboxylated S-adenosyl-L-methionine (dc-SAM), product of the reaction catalyzed by S-adenosyl-L-methionine decarboxylase (SAM-DC), with modifications in the side-chain portion of the molecule have been synthesized, and their ability to inhibit SAM-DC has been investigated. Mainly, compounds with a nitrogen atom in place of the sulfur were investigated. The data from these inhibition studies have resulted in a delineation of the structural features required for binding on SAM-DC. It was concluded that a terminal primary amino group, a terminal carboxyl group, and the sulfonium functionality are not required for binding on SAM-DC. It was also found that analogues of dc-SAM in which replacement of the sulfur by nitrogen was the only modification were still able to form an azomethine with the enzyme. As found for SAM and dc-SAM, these compounds also caused a time-dependent inactivation of SAM-DC.
D012437:Adenosylmethionine Decarboxylase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D002262:Carboxy-Lyases / Q000378:metabolism*; D055598:Chemical Phenomena; D002621:Chemistry; D004355:Drug Stability; D006207:Half-Life; D066298:In Vitro Techniques; D008099:Liver / Q000201:enzymology; D051381:Rats; D012436:S-Adenosylmethionine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D013997:Time Factors
D012436:S-Adenosylmethionine; D002262:Carboxy-Lyases; D012437:Adenosylmethionine Decarboxylase