STING ligand

STING activation with 2’3’-cGAMP

2’3’-cGAMP is a cyclic dinucleotide (CDN) that potently activates STING (stimulator of interferon genes). It is referred to as “noncanonical“ cGAMP due to the presence of the atypical 2’-5’ phosphodiester linkage between guanosine and adenosine. STING activation by 2’3’-cGAMP induces type I interferons (IFNs) and pro-inflammatory cytokines [1, 2]. STING is an endoplasmic adaptor and sensor protein that is paramount in innate immunity.

More details

Mode of action:

2’3’-cGAMP (cyclic [G(2’,5’)pA(3’,5’)p]) is produced in mammalian cells by cGAS (cGAMP synthase) in response to double-stranded DNA in the cytoplasm. Similar to the canonical 3’3’-cGAMP, 2’3’-cGAMP serves as a second messenger to activate innate immune responses by binding to and activating STING. Upon activation, STING induces type I IFNs, via the TANK-binding kinase 1 (TBK1)/ interferon regulatory factor 3 (IRF3) pathway [1], and pro-inflammatory cytokines, via the NF-κB pathway [1, 2].
Structural and functional studies revealed that 2’3’-cGAMP is distinct from the canonical 3’3’-cGAMP produced by bacteria [3, 4]. 2'3'-cGAMP binds to STING with a much greater affinity than 3'3'-cGAMP [1]. Interestingly, certain variants of STING are able to distinguish between noncanonical and canonical cGAMP [3].

Key features of 2’3’-cGAMP:

Potent STING agonist
Noncanonical CDN
Each lot is highly pure (≥95%) and functionally tested

Read our review on STING: Deciphering the STING Paradox

References:

1. Zhang X. et al., 2013. Cyclic GMP-AMP containing mixed phosphdiester linkages is an endogenous high-affinity ligand for STING. Mol Cell.51(2):226-35.
2. Abe T. & Barber G.N., 2014. CytosolicDNA-mediated, STING-dependent proinflammatory gene induction necessitates canonical NF-κB activation through TBK1. J Virol. 88(10):5328-41.
3. Diner E. et al., 2013. The Innate Immune DNA Sensor cGAS Produces a Noncanonical Cyclic Dinucleotide that Activates Human STING. Cell Rep. 3(5):1355-61.
4. Gao P. et al., 2013. Cyclic [G(2',5')pA(3',5')p] is the metazoan second messenger produced by DNA-activated cyclic GMP-AMP synthase. Cell. 153(5):1094-107.

2'3'-cGAMP

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