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Research ArticleArticle

Inhibition of Thymidylate Synthetase by Some Analogs of Tetrahydrofolic Acid

KAREL SLAVIK and SIGMUND F. ZAKRZEWSKI
Molecular Pharmacology July 1967, 3 (4) 370-377;
KAREL SLAVIK
Roswell Park Memorial Institute, Department of Experimental Therapeutics, New York State Department of Health, Buffalo, New York 14203
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SIGMUND F. ZAKRZEWSKI
Roswell Park Memorial Institute, Department of Experimental Therapeutics, New York State Department of Health, Buffalo, New York 14203
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Abstract

A series of derivatives of tetrahydrofolate and dihydrofolate were investigated as substrates or inhibitors of thymidylate synthetase. N10-Methyltetrahydrofolate is a competitive inhibitor of the enzyme, KI = 6.3 x 10-5 M. All other analogs tested inhibited in either a noncompetitive or uncompetitive manner. The relationship between the structure and the activities of the analogs as substrates or inhibitors is discussed.

ACKNOWLEDGMENTS The work reported in this paper was undertaken during the tenure of an Eleanor Roosevelt Cancer Fellowship awarded to Dr. Karl Slavik by the International Union Contra Cancer and supported by the U.S.P.H.S. grant CA-02906. The authors are indebted to Dr. Charles A. Nichol and Dr. Alexander Bloch for many helpful suggestions in the course of this study.

  • Copyright ©, 1967, by Academic Press Inc.

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Molecular Pharmacology
Vol. 3, Issue 4
1 Jul 1967
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Research ArticleArticle

Inhibition of Thymidylate Synthetase by Some Analogs of Tetrahydrofolic Acid

KAREL SLAVIK and SIGMUND F. ZAKRZEWSKI
Molecular Pharmacology July 1, 1967, 3 (4) 370-377;

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Research ArticleArticle

Inhibition of Thymidylate Synthetase by Some Analogs of Tetrahydrofolic Acid

KAREL SLAVIK and SIGMUND F. ZAKRZEWSKI
Molecular Pharmacology July 1, 1967, 3 (4) 370-377;
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