Cyclic di-GMP

Cyclic di-GMP (CAS: 61093-23-0) is a broadly distributed cyclic dinucleotide second messenger in bacteria. It couples two guanylates through two 3′5′ phosphodiester bonds in a head-to-tail cyclization. It also acts as a STING agonist and belongs, with cGAMP, to the cyclic dinucleotide family.

In host cells, cyclic di-GMP binds the STING ligand-binding domain, driving STING dimerization and translocation to the Golgi, where STING recruits and activates TBK1; TBK1 phosphorylates IRF3 and IKKβ to launch type I interferon and NF-κB pathways. In bacteria, cyclic di-GMP regulates biofilm formation, motility, and virulence; its identity as a STING ligand lets the host read this bacterial cyclic dinucleotide as an infection signal.

Cyclic di-GMP serves as a STING agonist and is often encapsulated in delivery systems such as liposomes for tumor immunotherapy and vaccine adjuvants; it also works as a research tool for activating STING with a microbial cyclic dinucleotide.

References:

Burdette DL, Sasaki Y, Deng W, et al. STING is a direct innate immune sensor of cyclic di-GMP. Nature. 2011;478(7370):515-518.

Nakamura T, et al. Liposomes loaded with a STING pathway ligand, cyclic di-GMP, enhance cancer immunotherapy against metastatic melanoma. J Control Release. 2015;216:149-157.