核苷及其类似物的三磷酸化方法研究进展  

Advances in Triphosphorylation of Nucleosides and Their Analogues

作　　者：任丽霞 贺万丽 赵佩佩[1] 蔡岩[1] Ren Lixia;He Wanli;Zhao Peipei;Cai Yan(Tianjin International Joint Academy of Biomedicine,Tianjin,300457;College of Pharmacy,Nankai University,Tianjin,300071)

机构地区：[1]天津国际生物医药联合研究院,天津300457 [2]南开大学药学院,天津300071

出　　处：《化学通报》2023年第1期42-54,41,共14页Chemistry

摘　　要：三磷酸核苷是一种具有三个磷酸基团的核苷酸,不仅在细胞的能量代谢中起着重要作用,也可用于心脑血管和神经系统等许多疾病的治疗和辅助治疗,随着分子生物学的发展,三磷酸核苷在许多生物检测技术中也应用广泛。新冠疫情爆发以来,抗病毒核苷类药物成为研究的热点,这类药物大多在体外不具有活性,而是在细胞内代谢为三磷酸形式发挥作用,在对这类化合物的抗病毒机理研究中,研究其抗病毒活性、抗病毒机制等都需要将核苷类药物进行三磷酸化,因此开发一种高效的核苷三磷酸化方法是十分必要的。本文根据三磷酸核苷的合成历史进程,综述了迄今为止三磷酸核苷的化学合成方案。旨在为核苷及其类似物的三磷酸化以及相关药物的研发提供参考。Nucleoside triphosphate are nucleosides with three phosphate groups, which not only play an important role in energy metabolism of cells, but also can be used in the treatment and adjuvant treatment of many diseases, such as cardiovascular and cerebrovascular diseases, blood diseases and neurological diseases. With the development of molecular biology, they are also widely used in many biological detection technologies. Since the outbreak of COVID-19, the research of antiviral nucleoside drugs has become a hot spot. Most of these drugs have no activity in vitro, but are metabolized to their triphosphate form in cell to take effect. In the research of mechanism of these nucleoside antiviral drugs, triphosphorylated nucleosides are required to study the antiviral activity and mechanism of drugs. Therefore, it is necessary to develop an efficient method of nucleoside triphosphorylation. According to the synthetic history of nucleoside triphosphates, the chemical synthetic strategies of nucleoside triphosphates are reviewed in this paper. The aim is to provide useful references for the triphosphorylation of nucleosides and their analogues, and also to provide some useful idea to the development of novel antiviral drugs.

关 键 词：三磷酸核苷 活性中间体 化学合成 抗病毒药物 

分 类 号：Q503[生物学—生物化学]