3'3'-cGAMP Fluorinated - STING Agonist

STING Ligand - Difluoro 3'3'-cGAMP, cyclic [FdG(3’,5’)pFdA(3’,5’)p]

3’3’-cGAMP Fluorinated (c-[2'FdGMP]-[2'FdAMP]) is a synthetic analog of cyclic guanosine monophosphate- adenosine monophosphate (cyclic GMP-AMP, cGAMP) with a fluorine atom at 2’ position of the nucleosides. 3’3’-cGAMP is a cyclic di-nucleotide produced by bacteria. It is also referred to as "canonical" cGAMP due the presence of the classical 3’-5’ phosphodiester linkages between the guanosine and the adenosine. It has been reported that cGAMP binds STING (stimulator of IFN genes) and subsequently induces TBK1-IRF3-dependent production of IFN-β [1].

The incorporation of fluorine into biologically active molecules is commonly used in medicinal chemistry to improve their metabolic stability or to modulate physicochemical properties such as lipophilicity [2, 3]. Moreover, the introduction of a fluorine atom can change the biological activities of a molecule. Interestingly, when used at low concentrations in various cellular assays, 3’3’-cGAMP Fluorinated induces higher levels of type I IFNs than does cGAMP.

STING ligands such as cGAMP induce type I IFNs and activate interferon stimulated genes (ISG) through IRFs. To facilitate their study, InvivoGen has developed stable reporter cells in two well established immune cell models: THP-1 human monocytes and RAW 264.7 murine macrophages. These cells express a reporter gene (SEAP or Lucia luciferase), under control of an IRF-inducible promoter.

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. Liu P. et al., 2008. Fluorinated Nucleosides: Synthesis and biological implication. J Fluor Chem. 129(9): 743–766.
3. Böhm HJ. et al., 2004. Fluorine in medicinal chemistry. Chembiochem. 5(5):637-43.