Biomaterial Database

5-[(4-Methyl-1,2,3,4-tetrahydroquinoxalyl)methyl]-2'-deoxyuridine 5'-phosphate: an analogue of a proposed intermediate in thymidylate synthetase catalysis. 1979

J S Park, and C T Chang, and M P Mertes

In a study of the sequence steps involved in the mechanism of thymidylate synthetase catalysis, 5-[(N-methyl-piperazinyl)methyl]- (5) and 5-[(4-methyl-1,2,3,4-tetrahydroquinoxalyl)methyl]-2'-deoxyuridine 5'-phosphate (6) were synthesized. Compound 6 has high affinity for the Lactobacillus casei enzyme (Ki = 0.75 microM, KI/Km - 0.23), which is 50 times stronger than that of the piperazinyl derivative 5. Compound 6, a possible multisubstrate inhibitor, is an analogue of a proposed intermediate in the reaction mechanism wherein the enzyme is eliminated from the covalent complex (enzyme--substrate--cofactor) prior to the redox reaction leading to the products 2'-deoxythymidine 5'-phosphate and 7,8-dihydrofolic acid.

UI	MeSH Term	Description	Entries
D007780	Lacticaseibacillus casei	A rod-shaped bacterium isolated from milk and cheese, dairy products and dairy environments, sour dough, cow dung, silage, and human mouth, human intestinal contents and stools, and the human vagina. L. casei is CATALASE positive.	Lactobacillus casei
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
D011810	Quinoxalines		Quinoxaline
D003856	Deoxyuracil Nucleotides	Uracil nucleotides which contain deoxyribose as the sugar moiety.	Deoxyuridine Phosphates,Nucleotides, Deoxyuracil,Phosphates, Deoxyuridine
D013940	Thymidylate Synthase	An enzyme of the transferase class that catalyzes the reaction 5,10-methylenetetrahydrofolate and dUMP to dihydrofolate and dTMP in the synthesis of thymidine triphosphate. (From Dorland, 27th ed) EC 2.1.1.45.	Thymidylate Synthetase,Synthase, Thymidylate,Synthetase, Thymidylate