ProTide技术研究进展及其在抗病毒药物研究领域中的应用  

Research progress of ProTide technology and its application in the development of antiviral drugs

作　　者：周慧宇 朱梅[1] 王玉成[1] ZHOU Hui-yu;ZHU Mei;WANG Yu-cheng(Institute of Medicinal Biotechnology,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China)

机构地区：[1]中国医学科学院、北京协和医学院医药生物技术研究所,北京100050

出　　处：《药学学报》2023年第6期1540-1556,共17页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(82204207)。

摘　　要：ProTide技术是由Christopher McGuigan团队开发的一种前药设计策略,其特征是将核苷类似物以磷(膦)酰化的方式引入芳氧基和氨基酸酯,形成芳氧基磷(膦)酰胺酯前药。ProTide技术能够使核苷类似物高效透过细胞膜并避开单磷酸化限速步骤,有效解决了核苷类药物难以被细胞摄取、磷酸化效率低等问题。目前, ProTide技术已广泛应用于抗病毒药物研发领域,孕育出了包括sofosbuvir在内的多款抗病毒重磅药物以及临床候选药物,对小分子抗病毒药物的研发进程产生了重要影响。本文对ProTide技术的发展历程及其特点进行了简要介绍,并概述了近年来ProTide技术在抗病毒药物研究领域的应用情况,期望为后续抗病毒药物的设计与开发提供参考。ProTide technology is a kind of prodrug design strategy invented by the team of Christopher McGuigan.ProTides are aryloxyphosphoramidates(or aryloxyphosphonamidates)which contain a phosphorus atom combined with an amino acid ester and an aryloxy group.These prodrugs can efficiently cross the cell membrane and escape from the first rate-limiting step of phosphorylation,which afford effective solutions to the drawbacks of current nucleoside analogues.At present,ProTide technology has been extensively applied in the field of antiviral research.It has been successful in providing a number of approved drugs and clinical candidates,such as sofosbuvir and so much more,highlighting the promising future in drug discovery.This review summarizes the brief history and characteristics of ProTide technology,as well as its application in the exploration of antiviral drugs.

关 键 词：ProTide 药物设计 前药 磷(膦)酰胺酯 抗病毒 

分 类 号：R914[医药卫生—药物化学]