3'3'-cGAMP

STING Ligand. Cyclic [G(3’,5’)pA(3’,5’)p]

3’3’-cGAMP (cyclic [G(3’,5’)pA(3’,5’)p], previously known as cGAMP) is a cyclic di-nucleotide produced by bacteria. 3’3’-cGAMP is also referred to as "canonical" cGAMP due the presence of the classical 3’-5’ phosphodiester linkages between the guanosine and the adenosine.

Recently, 3’3’-cGAMP was reported to bind STING (stimulator of IFN genes) and subsequently induce TBK1-IRF3-dependent production of IFN-β [1]. Studies in bacteria revealed that 3’3’-cGAMP serves as a second messenger and plays a role in bacterial chemotaxis and colonization [2].

Structural and functional studies revealed that the canonical 3’3’-cGAMP produced by bacteria is distinct from the noncanonical 2’3’-cGAMP produced by mammalian cGAS [3]. Certain variants of STING are able to distinguish between canonical and noncanonical cGAMP [4].

3’3’-cGAMP is more potent in activating IRF3 than c-di-AMP and c-diGMP, other 3',5' cyclic dinucleotides that also bind to STING [5].

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. Davies B. et al., 2012. Coordinated regulation of accessory genetic elements produces cyclic di-nucleotides for V. cholerae virulence. Cell. 149(2):358-70.)
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.
4. 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.
5. Burdette D. et al., 2011. STING is a direct innate immune sensor of cyclic di-GMP. Nature. 478(7370):515-8.

Figures

THP1-Dual™ cells were stimulated for 24 hours with the STING ligands as shown (all at 10 μg/ml). The interferon regulatory factor (IRF) response was assessed by measuring the activity of Lucia luciferase in the supernatant using QUANTI-Luc™ 4 Lucia/Gaussia. Data are shown in fold response over non-induced cells (mean ± SEM).

THP1-Dual™ cells were stimulated for 24 hours with the STING ligands as shown (all at 10 μg/ml). The NF-κB-induced SEAP activity was assessed using QUANTI‑Blue™ Solution, a SEAP detection reagent. Data are shown as optical density (OD) at 630 nm (mean ± SEM). Non‑induced cells (NI) have been included as a negative control.

Specifications

Description: STING agonist

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

CAS number: 849214-04-6

Formula: C₂₀H₂₂N₁₀O₁₃P₂ •2Na

Molecular weight: 718.38 g/mol

Purity: ≥ 95% by LC/MS

Solubility: 50 mg/ml in water

Quality control:

• The biological activity has been confirmed by measuring the induction of the interferon pathway in cellular assays.
• The absence of endotoxins and other bacterial contaminants has been confirmed using HEK-Blue™ TLR4 and HEK-Blue™ TLR2 cells.

Contents

• 500 µg or 1 mg (2 x 500 µg) or 2.5 mg (5 x 500 µg) lyophilized 3’3’-cGAMP (formerly called cGAMP)
• 1.5 ml endotoxin-free water

Product is shipped at room temperature

Product should be stored at -20°C. Product is sterile filtered prior to lyophilization.

Details

Structure of 3'3'-cGAMP