c-di-GMP Fluorinated - STING Agonist

STING Ligand - Difluoro 3'3'-c-di-GMP, cyclic [FdG(3’,5’)pFdG(3’,5’)p]

c-di-GMP Fluorinated (c-di[2’FdGMP]) is a synthetic analog of cyclic diguanylate monophosphate (c-di-GMP) with a fluorine atom at 2’ position of the nucleoside. c-di-GMP is a bacterial second messenger that acts a potent immunostimulant in mammals. It induces production of type I interferons (IFNs) by directly binding to the endoplasmic reticulum-resident receptor STING (stimulator of interferon genes) [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, c-di-GMP Fluorinated induces higher levels of type I IFNs than does c-di-GMP.

References:

1. Burdette DL. et al., 2011. STING is a direct innate immune sensor of cyclic di-GMP. Nature. 478(7370):515-8.
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.