2'3'-cGAMP - STING Agonist

Cyclic [G(2’,5’)pA(3’,5’)p]

ABOUT

2'3'-cGAMP mammalian cyclic di-nucleotide - STING ligand

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.

All InvivoGen products are for research use only, and not for human or veterinary use.

Also available:

High-quality pre-clinical grade

2'3'-cGAMP VacciGrade™

SPECIFICATIONS

Specifications

Synonyms
2'3'-Cyclic GMP-AMP disodium salt
Guanosine-Adenosine 2',3'-cyclic monophosphate disodium salt
Cyclic [G(2’,5’)pA(3’,5’)p] disodium salt
CAS number
2734858-36-5
Chemical formula

C20H22N10O13P2 •2Na

Molecular weight
718.38 g/mol
Working concentration

0.1 - 100 µg/ml

Purity
Purity (≥ 95%) validated by LC/MS and NMR
Solubility

50 mg/ml in water

Appearance (form)
Lyophilized
Reconstitution buffer
Endotoxin-free water (provided)
Sterility

0.22 µm filtration

Endotoxin

The absence of bacterial contamination (e.g. lipoproteins and endotoxins) is confirmed using HEK-Blue™ TLR2 and HEK-Blue™ TLR4 cells.

Applications

Induction of ISG and NF-κB pathways in cellular assays

Quality control

Each lot is released only after meeting predefined biological activity specifications in a cell-based assay.

CONTENTS

Contents

  • Product: 
    2’3’-cGAMP
  • Cat code: 
    tlrl-nacga23-02
  • Quantity: 
    200 µg
Includes:

1.5 ml endotoxin-free water

Shipping & Storage

  • Shipping method:  Room temperature

    • Storage:

    • -20°C

    Caution:

    • Avoid repeated freeze-thaw cycles

Details

STING

The STimulator of INterferon Genes STING, alternatively known as MPYS, TMEM173, MITA, and ERIS, is a key sensor of cytosolic nucleic acids. Initially thought to serve solely as an adaptor protein for mediating signaling by cytosolic DNA sensors (CDS), STING was found to be a direct sensor of cyclic dinucleotides (CDNs) [1].

 

STING signaling

CDNs are ubiquitous second-messenger molecules in bacterial or metazoal signal transduction and are defense triggers in mammalian cells. Namely, cyclic diguanylic acid (c-di-GMP), cyclic diadenylic acid (c-di-AMP), and cyclic adenylicguanylic acid (cGAMP) are the most prevalent intracellular signaling intermediates in bacteria and/or metazoa [2-3].

A direct interaction between DNA and STING could not be demonstrated, suggesting the intervention of at least one additional protein [1]. The identity of the major dsDNA cytosolic sensor was resolved in 2013: cGAs (cyclic GMP-AMP synthase) is activated upon direct DNA binding and subsequently catalyzes the production of a non-canonical cGAMP, which in turn, activates STING [3].

Once activated, STING and TANK-binding-kinase-I (TBK1) interact to induce an active interferon regulatory factor (IRF3) dimer which then binds to interferon-stimulated responsive elements (ISRE) in the nucleus and leads to IFN-α/β production [4]. The production of NF-κB-dependent inflammatory cytokines is also observed downstream of STING activation but the underlying mechanisms remain opaque [5].

 

References:

1. Burdette DL. et al., 2011. STING is a direct innate immune sensor of cyclic di-GMP. Nature 478(7370):515-8.
2. Woodward JJ. et al., 2010. c-di-AMP secreted by intracellular Listeria monocytogenes activates a host type I interferon response. Science 328(5986):1703-5.
3. Wu J. et al., 2013. Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA. Science, 339(6121):826-30.
4. Ishikawa H. et al., 2009. STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity. Nature 461: 788-92.
5. Abe T. and Barber G.N., 2014. Cytosolic-DNA-Mediated, STING-Dependent Proinflammatory Gene Induction Necessitates Canonical NF-κB Activation through TBK1. Journal of Virology 88:5328-41.

DOCUMENTS

Documents

2’3’-cGAMP

Technical Data Sheet

Validation Data Sheet

Safety Data Sheet

Certificate of analysis

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