SYNTHESIS AND INTERACTION WITH THYMIDYLATE SYNTHASE OF 5'-DITHIOPHOSPHATE AND 5'-FLUOROTHIOPHOSPHATE OF THYMIDINE

Thymidine-5'-fluorothiophosphate, dTMP(S)-F, was synthesized by the ox athiaphospholane, and thymidine 5'-dithiophosphate, dTMPS(2), by the d ithiaphospholane, method. To estimate the role of 5'-phosphate group i onization in binding of pyrimidine nucleotides by thymidylate synthase , dTMP(S)-F was studied as an inhibitor of mouse tumour (L1210) enzyme , and its inhibitory properties were compared with those of dTMPS(2), a close dTMP analogue. While dTMPS(2) proved to be an inhibitor, compe titive vs dUMP, with K-i(app) = 94 mu M, the 5'-fluorothiophasphate co ngener displayed no activity, indicating that the enzyme requires for binding the presence of a dianionic 5'-phosphate group in a nucleotide .