115827-03-7Relevant articles and documents
A pyrimidine-based 'flexible' bisubstrate analogue inhibitor of human thymidylate synthase
Yang,Slusher,Broom,Ueda,Cheng
, p. 2126 - 2132 (2007/10/02)
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 compounds are shown to be potent competitive inhibitors with respect to dUMP or 5,10-CH2-H4PteGlu but gave mixed kinetics with respect to 5,10-CH2-H4PteGlu5 for human thymidylate synthase.