Rational design of selective antimetabolites of DNA-thymine biosynthesis: 5-propynylpyrimidine nucleoside derivatives

Authors
Kalman, TI Nie, Z
Citation
Ti. Kalman et Z. Nie, Rational design of selective antimetabolites of DNA-thymine biosynthesis: 5-propynylpyrimidine nucleoside derivatives, NUCLEOS NUC, 19(1-2), 2000, pp. 357-369
Citations number
21
Categorie Soggetti
Biochemistry & Biophysics
Journal title
NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS
ISSN journal
15257770 → ACNP
Volume
19
Issue
1-2
Year of publication
2000
Pages
357 - 369
Database
ISI
SICI code
1525-7770(2000)19:1-2<357:RDOSAO>2.0.ZU;2-L
Abstract
A novel series of 5-propynylpyrimidine nucleosides are proposed as potentia l antimetabolites of DNA-thymine biosynthesis. This proposal is based on th e results of detailed mechanistic analyses of the molecular interactions be tween dTMP synthase and its inhibitors. It is proposed that a propynyl side -chain at the 5-position of dUMP, bearing an appropriate leaving group, wou ld cause irreversible inactivation of dTMP synthase, which would not requir e the presence of the cofactor, CH(2)H(4)folate.