Gołos B, Misiura K, Olesiak M, Okruszek A, Stec W J, Rode W
Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw.
Acta Biochim Pol. 1998;45(1):83-6.
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.
通过氧硫磷杂环戊烷合成了胸苷-5'-氟硫代磷酸酯（dTMP(S)-F），并通过二硫磷杂环戊烷法合成了胸苷5'-二硫代磷酸酯（dTMPS2）。为了评估5'-磷酸基团离子化在胸苷酸合酶结合嘧啶核苷酸中的作用，对dTMP(S)-F作为小鼠肿瘤（L1210）酶抑制剂进行了研究，并将其抑制特性与结构相近的dTMP类似物dTMPS2的抑制特性进行了比较。虽然dTMPS2被证明是一种对dUMP具有竞争性的抑制剂，表观抑制常数（K(i)app）为94微摩尔，但5'-氟硫代磷酸酯类似物没有活性，这表明该酶结合核苷酸时需要二价阴离子形式的5'-磷酸基团。
