环二核苷酸类似物研究进展

Research progress of cyclic dinucleotide analogues

环二核苷酸是由两个核苷单磷酸通过两个磷酸二酯键连接而成的环状分子.环二核苷酸最早在细菌中被发现,是细菌中普遍存在的第二信使,在调节细菌的生理功能和抗噬菌体感染等方面发挥重要作用.人体免疫系统在病原核酸的刺激下可合成环二核苷酸,该分子作为第二信使与干扰素基因刺激因子(STING)结合,激活下游信号通路,并最终诱导干扰素分泌,启动抗感染免疫响应.环二核苷酸及其类似物是感染性疾病及肿瘤免疫治疗的先导化合物,也是具有良好应用前景的免疫佐剂.对环二核苷酸的发现、环二核苷酸的生物功能等进行了简单回顾,总结了环二核苷酸结构修饰的基本策略及环二核苷酸类似物的结构多样性.

Cyclic dinucleotide(CDN)is a kind of macrocyclic molecules composed of two nucleoside monophosphates linked with two phosphodiester bonds.CDNs were firstly found in bacteria as second messengers to regulate many physiological functions and mediate antiphage response of bacteria.In response to exotic or intrinsic abnormal nucleic acid,human immune system can synthesize non-canonical CDN,which binds with stimulator of interferon genes(STING)to initiate the cascade of signal pathways to produce type I interferon,and activate immune responses.CDN and its analogues are agonists of STING,and have been involved in infectious diseases,tumor and autoimmune diseases.This article provided a brief review of the discovery and biofunctions of CDNs,and focused on the strategies of CDN structural modifications and structural diversity of CDN analogues.