T. Kalman, Z. Nie, A. Kamat
Feb 21, 2000
Citations
0
Influential Citations
4
Citations
Journal
Bioorganic & medicinal chemistry letters
Abstract
5-Fluoropropynyl-2'-deoxyuridine 5'-phosphate (3) was designed as a mechanism-based inactivator of thymidylate synthase (TS). The inhibitor was synthesized from 5-iodo-2'-deoxyuridine and propargyl alcohol by palladium-catalyzed coupling, followed by fluorination and selective phosphorylation. Incubation of TS with 3, in the presence or absence of the CH2H4folate cofactor, caused rapid, irreversible inactivation of the enzyme.