Thavoncharoensub Ninticha, Maruyama Kento, Heh Choon Han, Hoong Leong Kok, Shi Hui, Shigematsu Yoshiharu, Sasaki Shigeki, Taniguchi Yosuke
a Department of Medicinal Sciences , Graduate School of Pharmaceutical Sciences, Kyushu University , Higashi-ku , Fukuoka , Japan.
b Department of Pharmacy , Faculty of Pharmacy, Mahidol University , Bangkok , Thailand.
Nucleosides Nucleotides Nucleic Acids. 2019;38(8):578-589. doi: 10.1080/15257770.2019.1586919. Epub 2019 Mar 31.
8-OxodGTP is generated by the reaction between dGTP and reactive oxygen species and a considered mutagenic nucleotide. It can be incorporated into the duplex DNA during replication processes by the DNA polymerase, and thus the repair enzyme removes oxodGTP from the nucleotide pools in living cells. On the other hand, the γ-modified triphosphates show interesting properties for use as biological tools. Therefore, the γ-N-pyrenylalkyl-oxodGTP derivatives were synthesized and their effect on the enzymatic reactions were evaluated. The γ-N-pyrenylmethyl-oxodGTP was found to be accepted by the DNA polymerase just like oxodGTP, but showed a competitive inhibition property for the human oxodGTPase.
8-氧代鸟嘌呤三磷酸（8-OxodGTP）由脱氧鸟苷三磷酸（dGTP）与活性氧反应生成，是一种具有诱变作用的核苷酸。在复制过程中，它可被DNA聚合酶掺入双链DNA中，因此修复酶会从活细胞的核苷酸池中清除氧代鸟嘌呤三磷酸。另一方面，γ-修饰的三磷酸酯作为生物工具具有有趣的特性。因此，合成了γ-N-芘基烷基-氧代鸟嘌呤三磷酸衍生物，并评估了它们对酶促反应的影响。发现γ-N-芘基甲基-氧代鸟嘌呤三磷酸与氧代鸟嘌呤三磷酸一样能被DNA聚合酶接受，但对人氧代鸟嘌呤三磷酸酶具有竞争性抑制特性。
