Biomolecular study of human thymidylate synthase conformer-selective inhibitors: New chemotherapeutic approach.

ABSTRACT: Thymidylate synthase (TS) is a well-validated target for the therapy of adult cancers. Propane-1,3-diphosphonic acid (PDPA) has significant inhibitory properties against human thymidylate synthase (hTS) relative to mouse TS which is not predicted to adopt an inactive conformer. The current research aims to identify novel, lead inhibitors of hTS and examine the prediction that they bind selectively to hTS enzymes existing in different conformational equilibria. Conformer-selectivity was evaluated through performing activity inhibition studies, as well as intrinsic fluorescence (IF) studies in comparison to the known orthosteric inhibitor raltitrexed (RTX). Human TS was isolated from recombinant bacteria expressing either native hTS, capable of conformational switching, or an actively stabil

SUBMITTER: El-Mesallamy HO 

PROVIDER: S-EPMC5851609 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature