Ono K, Ohashi A, Yamamoto A, Matsukage A, Takahasi T, Saneyoshi M, Ueda T
Cancer Res. 1979 Nov;39(11):4673-80.
The effects of the newly synthesized compound 9-beta-D-arabinofuranosylguanine 5'-triphosphate (ara-GTP) on the activity of DNA polymerases from mouse cells and oncornavirus were compared with those of 9-beta-D-arabinofuranosyladenine 5'-triphosphate. Ara-GTP did not replace deoxyguanosine 5'- triphosphate as substrate for these DNA polymerases but inhibited the activities of DNA polymerase alpha, beta, and gamma and viral DNA polymerase. DNA polymerase alpha was more sensitive than DNA polymerases beta and gamma and viral DNA polymerase to inhibition by ara-GTP. The inhibitions by ara-GTP and 9-beta-D-arabinofuranosyladenine 5'-triphosphate were due to competition or partial competition 5'-triphosphate were due to competition or partial competition with deoxynucleoside triphosphate with the same base. The inhibition constant (Ki) and the mode of inhibition of nucleotide incorporation varied depending on the combination of inhibitor, substrate(s), and enzyme species.
将新合成的化合物9-β-D-阿拉伯呋喃糖基鸟嘌呤5'-三磷酸(ara-GTP)对小鼠细胞DNA聚合酶和肿瘤病毒的活性影响,与9-β-D-阿拉伯呋喃糖基腺嘌呤5'-三磷酸的影响进行了比较。Ara-GTP不能替代脱氧鸟苷5'-三磷酸作为这些DNA聚合酶的底物,但会抑制DNA聚合酶α、β和γ以及病毒DNA聚合酶的活性。DNA聚合酶α比DNA聚合酶β、γ以及病毒DNA聚合酶对ara-GTP的抑制作用更敏感。Ara-GTP和9-β-D-阿拉伯呋喃糖基腺嘌呤5'-三磷酸的抑制作用是由于与具有相同碱基的脱氧核苷三磷酸竞争或部分竞争所致。抑制常数(Ki)和核苷酸掺入的抑制模式因抑制剂、底物和酶种类的组合而异。