2'3'-cGAMP

Description

2′,3′-cGAMP (CAS 1441190-66-4) is an endogenous STING (stimulator of interferon genes) agonist.1?Produced from ATP and GTP via the action of cGMP-AMP synthase (cGAS) which acts as a cytosolic DNA sensor.2,3?Induces autophagy which is a mechanism for clearance of DNA and viruses in the cytosol.4?DNA damage stimulates 2’,3’-cGAMP which stimulates an inflammatory response.5

The Uses of 2'3'-cGAMP

2′,3′-cGAMP sodium salt has been used to identify small compounds capable of binding human stimulator of interferon genes (STING). It is also used to study type I interferon response to cytosolic DNA.

Definition

ChEBI: 2'-3'-cGAMP is a cyclic purine dinucleotide that consists of AMP and GMP units cyclised via 3',5'- and 2',5'-linkages respectively. It is a cyclic purine dinucleotide, a guanyl ribonucleotide and an adenyl ribonucleotide. It is functionally related to a Gp[2'-5']Ap[3']. It is a conjugate acid of a 2'-3'-cGAMP(2-).

Biochem/physiol Actions

2′,3′-cGAMP (cyclic [G(2′,5′)pA(3′,5′)p]) is the natural agonist for the STING (STimulator of INterferon Genes) pathway, discovered to be a pathway for antiviral innate immunity. 2′3′-cGAMP is a second messenger produced in mammalian cells by the cytosolic DNA sensor cGAS (cGAMP synthase) to activate innate immune responses by binding to STING and initiating an interferon response. The affinity of 2′3′-cGAMP for human STING is much higher than that of the bacterial 3′3′-cyclic dinucleotides (CDNs), with a Kd of 4.59 nM compared to >1 μM for bacterial 3′3′-CDNs.

References

1) Zhang?et al.?(2015), Cyclic GMP-AMP containing mixed phosphodiester linkages is an endogenous high-affinity ligand for STING; Mol. Cell?51?226 2) Wu?et al.?(2013), Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA; Science?339?826 3) Sun?et al.?(2013), Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway; Science?339?786 4) Gui?et al.?(2019),?Autophagy induction via STING trafficking is a primordial function of the cGAS pathway;??Nature,?567?262 5) Li and Chen (2018),?The cGAS-cGAMP-STING pathway connects DNA damage to inflammation, senescence and cancer;??J. Exp. Med.,?215?1287