5-propynylpyrimidine nucleoside derivatives: rationally designed mechanism-based inactivators of thymidylate synthase.
Nucleosides Nucleotides Nucleic Acids
; 20(4-7): 869-71, 2001.
Article
in En
| MEDLINE
| ID: mdl-11563134
ABSTRACT
A novel series of 5-propynyl-dUMP derivatives, with a variety of leaving groups on the side-chain, was designed as potential mechanism-based inhibitors 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 Ki-values of 0.015-18 microM. Analogs with fluorine or imidazole-based leaving groups caused rapid, irreversible inactivation of TS.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Thymidylate Synthase
/
Deoxyuracil Nucleotides
/
Enzyme Inhibitors
Language:
En
Journal:
Nucleosides Nucleotides Nucleic Acids
Journal subject:
BIOQUIMICA
Year:
2001
Document type:
Article
Affiliation country:
United States