Probing the Thymidylate Synthase Active site with Bisubstrate Analog Inhibitors

Abstract Earlier reports on the enhancement of folate analog binding to thymidylate synthase (TS) by N10-propargylation prompted the synthesis of a bisubstrate analog containing an 8-deaza-N10-propargyl-5,6,7,8-tetrahydrofolate moiety coupled through a methylene linkage to 2′-deoxyuridylate.

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