Pomeisl Karel, Horská Květoslava, Pohl Radek, Blažek Jiří, Krečmerová Marcela
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v.v.i. , Prague, Czech Republic.
Nucleosides Nucleotides Nucleic Acids. 2012;31(3):159-71. doi: 10.1080/15257770.2011.648361.
A series of new monophosphates of 1-[2-(phosphonomethoxy)alkyl]thymines, such as PMPTp(,) 3-MeO-PMPTp, HPMPTp, and FPMPTp, were synthesized and tested for their ability to inhibit human thymidine phosphorylase. Kinetic measurements of enzyme activity were performed using thymidine and inorganic phosphate as the substrates. The data show that some monophosphates provide a considerable increase of the multisubstrate inhibitory effect. The highest inhibitory potency was found with (R)-FPMPTp 4c (K (i) (dT) = 4.09 ± 0.47 μM, K (i)(P(i)) = 2.13 ± 0.29 μM) and (R) 3-MeO-PMPTp 4d (K (i) (dT) = 5.78 ± 0.71 μM, K (i)(P(i)) = 2.71 ± 0.37 μM).
合成了一系列1-[2-(膦酰甲氧基)烷基]胸腺嘧啶的新型单磷酸盐，如PMPTp、3-MeO-PMPTp、HPMPTp和FPMPTp，并测试了它们抑制人胸苷磷酸化酶的能力。以胸苷和无机磷酸盐为底物进行酶活性的动力学测定。数据表明，一些单磷酸盐可显著增强多底物抑制作用。发现(R)-FPMPTp 4c（K(i)(dT)=4.09±0.47μM，K(i)(P(i))=2.13±0.29μM）和(R) 3-MeO-PMPTp 4d（K(i)(dT)=5.78±0.71μM，K(i)(P(i))=2.71±0.37μM）具有最高的抑制效力。
