5-propynylpyrimidine nucleoside derivatives: Rationally designed mechanism-based inactivators of thymidylate synthase

Authors
Kalman, TI Nie, Z Kamat, A
Citation
Ti. Kalman et al., 5-propynylpyrimidine nucleoside derivatives: Rationally designed mechanism-based inactivators of thymidylate synthase, NUCLEOS NUC, 20(4-7), 2001, pp. 869-871
Citations number
3
Categorie Soggetti
Biochemistry & Biophysics
Journal title
NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS
ISSN journal
15257770 → ACNP
Volume
20
Issue
4-7
Year of publication
2001
Pages
869 - 871
Database
ISI
SICI code
1525-7770(2001)20:4-7<869:5NDRDM>2.0.ZU;2-F
Abstract
A novel series of 5-propynyl-dUMP derivatives, with a variety of leaving gr oups on the side-chain, was designed as potential mechanism-based inhibitor s of thymidylate synthase (TS), and synthesized from 5-iodo-2'-deoxyuridine by Pd(0)-catalyzed coupling, followed by direct phosphorylation with POCl3 . All members of the series inhibited TS competitively with K-i-values of 0 .015-18 muM. Analogs with fluorine or imidazole-based leaving groups caused rapid, irreversible inactivation of TS.