A pyrimidine-based" flexible" bisubstrate analog inhibitor of human thymidylate synthase

IY Yang, RM Slusher, AD Broom, T Ueda…

Index: Yang; Slusher; Broom; Ueda; Cheng Journal of Medicinal Chemistry, 1988 , vol. 31, # 11 p. 2126 - 2132

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Citation Number: 9

Abstract

The synthesis and characterization of two “flexible” bisubstrate analogues of the intermediate in the thymidylate synthase reaction are reported. Steric constraints are minimized and diasteromeric mixtures avoided by using a pyrimidine-based analogue as the folate portion of the inhibitor while retaining all known important binding sites. A preliminary assessment of certain conformational parameters by NMR is presented. The ...