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. 1972 Jul;69(7):1855–1857. doi: 10.1073/pnas.69.7.1855

5-Fluoro-2′-Deoxyuridylate: Covalent Complex with Thymidylate Synthetase

Daniel V Santi 1, Charles S McHenry 1
PMCID: PMC426818  PMID: 4505665

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.

Keywords: affinity labeling, enzyme mechanism, inhibition, fluorinated pyrimidines

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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