Synthesis and interaction with thymidylate synthase of 5'-dithiophosphate and 5'-fluorothiophosphate of thymidine.

B Gołos; K Misiura; M Olesiak; A Okruszek; W J Stec; W Rode

doi:10.18388/abp.1998_4289

Synthesis and interaction with thymidylate synthase of 5'-dithiophosphate and 5'-fluorothiophosphate of thymidine.

B Gołos Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw.;
K Misiura
M Olesiak
A Okruszek
W J Stec
W Rode

DOI: https://doi.org/10.18388/abp.1998_4289

Abstract

Thymidine-5'-fluorothiophosphate, dTMP(S)-F, was synthesized by the oxathiaphospholane, and thymidine 5'-dithiophosphate, dTMPS2, by the dithiaphospholane, method. To estimate the role of 5'-phosphate group ionization 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 dTMPS2, a close dTMP analogue. While dTMPS2 proved to be an inhibitor, competitive vs dUMP, with K(i)app = 94 microM, the 5'-fluorothiophosphate congener displayed no activity, indicating that the enzyme requires for binding the presence of a dianionic 5'-phosphate group in a nucleotide.

Published

1998-03-31

Issue

Vol. 45 No. 1 (1998)

Section

Articles

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