Discovery of an acyclic nucleoside phosphonate that inhibits Mycobacterium tuberculosis ThyX based on the binding mode of a 5-alkynyl substrate analogue.

Abstract excerpt

The urgent need for new antibiotics poses a challenge to target un(der)exploited vital cellular processes. Thymidylate biosynthesis is one such process due to its crucial role in DNA replication and repair. Thymidylate synthases (TS) catalyze a crucial step in the biosynthesis of thymidine 5-triphosphate (TTP), an elementary building block required for DNA synthesis and repair. To date, TS inhibitors have only...

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