Résumé
The Stimulator of interferon genes (STING) protein plays a crucial role in the activation of the innate immune response. Activation of STING is initiated by cyclic dinucleotides (CDNs) which prompted the community to synthesize structural analogues to enhance their biological properties. We present here the synthesis and biological evaluation of four novel CDN analogues composed of an N-acylsulfonamide linkage. These CDNs were obtained in high overall yields via the sulfo-click reaction as a key step. Cyclic dinucleotides (CDNs) are crucial molecular cellular second messengers present in various organisms. In bacteria, they regulate diverse processes such as quorum sensing, signal transduction or control of biofilm formation. 1 While purine containing CDNs such as 3'5'-c-di-GMP, 3'5'-c-di-AMP, 2'3'-c-GAMP and 3'3'-c-GAMP (Figure 1), are the most studied, the recent discovery of c-di-UMP and c-UAMP in E. coli suggests that CDNs containing pyrimidine nucleobase are also biosynthesized.