2'3'-cGAMP

STING ligand

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.

2’3’-cGAMP is also referred to as “noncanonical“ cGAMP due to the presence of the atypical 2’-5’ phosphodiester linkage between the guanosine and the adenosine.

Similar to the canonical 3’3’-cGAMP, 2’3’-cGAMP serves as a second messenger to activate innate immune responses by binding to STING (stimulator of IFN genes) and subsequently inducing the TBK1-IRF3-dependent production of IFN-β [1]. 

Structural and functional studies revealed that noncanonical 2’3’-cGAMP is distinct from the canonical 3’3’-cGAMP produced by bacteria [2,3]. 2'3'-cGAMP binds to STING with a much greater affinity than 3'3'-cGAMP [1].

Certain variants of STING are able to distinguish between noncanonical and canonical cGAMP [2].

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. 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.
3. 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.

Figures

THP1-Dual™ cells were stimulated for 24 hours with the STING ligands as shown (all at 10 μg/ml). IRF induction was determined by measuring the relative light units (RLUs) in a luminometer using QUANTI‑Luc™, a Lucia luciferase detection reagent.

THP1-Dual™ cells were stimulated for 24 hours with the STING ligands as shown (all at 10 μg/ml). NF‑kB induction was determined using QUANTI‑Blue™, a SEAP detection reagent, and by reading the optical density (OD) at 655 nm. Non-induced cells (NI) have been included as a negative control.

Specifications

Description: STING agonist

Synonym: Cyclic [G(2’,5’)pA(3’,5’)p], cyclic GMP-AMP; c-GpAp sodium salt

CAS number: 1441190-66-4

Formula: C₂₀H₂₂N₁₀O₁₃P₂ •2Na

Molecular weight: 718.38

Purity: ≥ 95% by LC/MS

Solubility: 50 mg/ml in water

Quality control:

• The biological activity has been confirmed using cellular assays.
• The absence of endotoxins and other bacterial contaminants has been confirmed using HEK-Blue™ TLR4 and HEK-Blue™ TLR2 cells.

Contents

2’3’-cGAMP is provided as a lyophilized powder, the product is sterile filtered prior to lyophilization.

2’3’-cGAMP is available in three quantities:

• 200 µg 2’3’-cGAMP +  1.5 ml endotoxin-free water.
• 500 µg 2’3’-cGAMP +  1.5 ml endotoxin-free water.
• 1 mg (2 x 500 µg) 2’3’-cGAMP + 1.5 ml endotoxin-free water.
• 5 mg (5 x 1 mg) 2’3’-cGAMP + 10 ml endotoxin-free water.

2’3’-cGAMP is shipped at room temperature

2’3’-cGAMP should be stored at -20°C.