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Mechanism-based inactivation of thymidylate synthase by 5-(3-fluoropropyn-1-yl)-2'-deoxyuridine 5'-phosphate.

Authors
  • Kalman, T I
  • Nie, Z
  • Kamat, A
Type
Published Article
Journal
Bioorganic & Medicinal Chemistry Letters
Publisher
Elsevier
Publication Date
Feb 21, 2000
Volume
10
Issue
4
Pages
391–394
Identifiers
PMID: 10714507
Source
Medline
License
Unknown

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.

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