Open AccessSynthesis and interaction with thymidylate synthase of 5'-dithiophosphate and 5'-fluorothiophosphate of thymidine.
Author(s) -
Barbara Gołos,
Konrad Misiura,
Magdalena Olesiak,
And̀rzej Okruszek,
Wojciech J. Stec,
Wojciech Rode
Publication year - 1998
Publication title -
acta biochimica polonica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.452
H-Index - 78
eISSN - 1734-154X
pISSN - 0001-527X
DOI - 10.18388/abp.1998_4289
Subject(s) - thymidylate synthase , thymidine , nucleotide , chemistry , enzyme , phosphate , pyrimidine , biochemistry , stereochemistry , thymidine kinase , dna , biology , genetics , chemotherapy , fluorouracil , virus , herpes simplex virus , gene
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.