Basic Information
ID: ALA1121774
Journal: J Med Chem
Title: Interaction of 5-ethynyl-2'-deoxyuridylate with thymidylate synthetase.
Authors: Danenberg PV, Bhatt RS, Kundu NG, Danenberg K, Heidelberger C.
Abstract: The interaction of 5-ethynyl-2'-deoxyuridylate (5-ethynyl-dUMP; 1) with thymidylate (dTMP) synthetase has been investigated. The compound was an inhibitor of the enzyme, competitive with 2'-deoxyuridylate (dUMP) when the reaction was initiated by addition of enzyme (Ki = 2.7 X 10(-6) M). However, upon preincubation of 1 with dTMP synthetase, the inhibition pattern became noncompetitive. The time course of the enzyme reaction in the presence of 1 was nonlinear, indicating an increase in binding with time. Irreversible inactivation of the enzyme did not occur. The compound did not appear to become altered structurally as a result of interaction with the enzyme. A ternary complex was formed among dTMP synthetase, compound 1, and 5,10-methylenetetrahydrofolate, which was stable enough to survive Sephadex G-25 filtration but dissociated upon denaturation of the enzyme.
CiteXplore: 6796692
DOI: 10.1021/jm00144a036
Patent ID: ┄
Associated Items: Associated Bioactivities Associated Assays Associated Compounds Associated Targets