Home LiteratureArticle Details
PMID: 4505665 Published · ppublish English Journal Article

5-Fluoro-2'-deoxyuridylate: covalent complex with thymidylate synthetase.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 69 ·No. 7 ·1972-07-00 ·Pages 1855-7

Santi DV, McHenry CS

Abstract

5-Fluoro-2'-deoxyuridylate causes a rapid inactivation of thymidylate synthetase that is dependent upon prior complexation of the cofactor 5,10-methylenetetrahydrofolate. The enzyme-5-fluoro-2'-deoxyuridylate complex may be isolated on nitrocellulose membranes and is not disrupted by 6 M urea. Upon reaction of 5-fluoro-2'-deoxyuridylate with the enzyme in the presence of 5,10-methylenetetrahydrofolate a rapid loss of absorbance is observed at 269 nm, the absorption maximum for the pyrimidine chromophore. It is concluded that a covalent bond is formed between the 6-position of 5-fluoro-2'-deoxyuridylate and a nucleophilic group of the enzyme that is involved in catalysis.

MeSH Terms
Chemical Phenomena Chemistry Deoxyribonucleotides Filtration Fluorine Lactobacillus/enzymology Methyltransferases/antagonists & inhibitors Protein Binding Spectrophotometry Tetrahydrofolates Thymine Nucleotides Tritium Ultraviolet Rays Uracil Nucleotides Urea
Chemicals
Deoxyribonucleotides Tetrahydrofolates Thymine Nucleotides Uracil Nucleotides Tritium Fluorine Urea Methyltransferases
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Santi D V
McHenry C S
References (15)
15 references, click to expand
  1. Fluorinated pyrimidines. XXVI. Mammalian thymidylate synthetase: its mechanism of action and inhibition by fluorinated nucleotides.
    Mol Pharmacol. 1965 Jul;1(1):14-30 PMID: 4220791
  2. The mechanism of the condensation of formaldehyde with tetrahydrofolic acid.
    J Biol Chem. 1966 Dec 25;241(24):5851-63 PMID: 5954363
  3. An exchange between the hydrogen atom on carbon 5 of deoxyuridylate and water catalyzed by thymidylate synthetase.
    J Biol Chem. 1967 Mar 25;242(6):1302-6 PMID: 5337157
  4. Tetrahydrofolate-dependent labilization of the hydrogen atom on carbon 5 of 5'-deoxycytidylate, a step in the deoxycytidylate hydroxymethylase reaction.
    J Biol Chem. 1967 Mar 25;242(6):1307-13 PMID: 5337158
  5. Nucleosides XXXVI. Transformation of arabinopyrimidine nucleosides.
    Tetrahedron Lett. 1966 Oct;40:4927-34 PMID: 5977305
  6. Model studies of thymidylate synthetase. Neighboring-group facilitation of electrophilic substitution reactions of uracil furanosides.
    J Am Chem Soc. 1968 Oct 23;90(22):6236-8 PMID: 5696276
  7. Nucleosides. 58. Transformations of pyrimidine nucleosides in alkaline media. 3. The conversion of 5-halogenouridines into imidazoline and barbituric acid nucleosides.
    J Org Chem. 1969 May;34(5):1390-6 PMID: 5786172
  8. On the properties and utility of a membrane filter assay in the study of isoleucyl-tRNA synthetase.
    Anal Biochem. 1970 Jun;35(2):450-65 PMID: 5271039
  9. Small-scale preparation of 5'-nucleotides and analogs by carrot phosphotransferase.
    Anal Biochem. 1970 Aug;36(2):413-21 PMID: 5452962
  10. Properties of thymidylate synthetase from dichloromethotrexate-resistant Lactobacillus casei.
    J Biol Chem. 1970 Oct 25;245(20):5292-6 PMID: 4918842
  11. Inhibition of thymidylate synthetase by 5-formyl- and 5-hydroxymethyl-2'-deoxyuridylate.
    Biochem Biophys Res Commun. 1971 Mar 5;42(5):813-7 PMID: 4929928
  12. Crystalline thymidylate synthetase from dichloromethotrexate resistant Lactobacillus casei.
    Prep Biochem. 1971 Jan;1(1):47-54 PMID: 5003635
  13. Thymidylate synthetase. Model studies of inhibition by 5-trifluoromethyl-2'-deoxyuridylic acid.
    Biochemistry. 1971 Sep 14;10(19):3598-607 PMID: 5146573
  14. Nucleotide interconversions. II. Elevation of deoxycytidylate deaminase and thymidylate synthetase in regenerating rat liver.
    J Biol Chem. 1960 Oct;235:2968-70 PMID: 13765762
  15. The enzymatic synthesis of thymidylate. I. Early steps in the purification of thymidylate synthetase of Escherichia coli.
    J Biol Chem. 1962 Dec;237:3794-801 PMID: 13998281
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.69.7.1855
Published
1972-07-00
Pages
1855-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC426818
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.69.7.1855 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2