环二鸟苷酸(c-di-GMP)是一种重要的第二信使,其不仅参与调控多种细菌生理活动,还能够激活哺乳动物天然免疫信号通路诱导Ⅰ型干扰素等的释放.本文报道了利用亚磷酰胺一釜环合法,合成了无环鸟苷修饰的c-di-GMP及其磷硫代类似物(7a,7b,7c),发现其诱导小鼠巨噬细胞释放Ⅰ型干扰素的活性完全丧失,表明c-di-GMP的糖环结构对其保持激活STING信号通路的能力至关重要.“,”C-di-GMP is one kind of second messengers which plays an important role not only in the regulation of various bacterial physiological activities but also in the activation of innate immune response to induce type Ⅰ interferon in mammalian cells.In this assay,by using one-pot phosphoramidite method,three novel kinds of analogs of c-di-GMP including its phosphorthiates modified by ganciclovir (7a,7b,7c) have been designed and synthesized.The immune-stimulatory results of these c-di-GMP analogs in RAW-Lucia ISG cells indicated that they couldn't induce the release of type Ⅰ interferon,which demonstrated that the intact structure of ribose moieties is very vital for their bioactivity upon the activation of STING signaling pathway.