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Cyclic di-GMP is a second messenger in bacteria involved in diverse prokaryotic processes, including biofilm formation, motility, virulence, and cell cycling.[1],[2] In eukaryotic cells, cyclic di-GMP is detected by and binds to the transmembrane protein stimulator of interferon genes (STING; Kd = 1.21 μM), leading to activation of the innate immune system.[3],[4] It has been used at a preset molar ratio with STING dimers in binding assays to determine the binding constants of particularly tight binding partners, such as 2’3’-cGAMP. Cyclic di-GMP induces IFN-β mRNA expression in vitro (EC50 = 537.8 nM) but less potently than 2’3’-cGAMP, 3’2’-cGAMP, 3’3’-cGAMP, and 2’2’-cGAMP.

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