c-di-GMP

STING Ligand. Bacterial cyclic di-nucleotide

Bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP) is a second messenger produced in bacteria but not in mammals. This cyclic dinucleotide is involved in complex biological processes, such as biofilm formation, virulence and photosynthesis.

Besides its role as an intracellular and intercellular signaling molecule in prokaryotes, c-di-GMP also affects eukaryotes.

In mammals, c-di-GMP is recognized by STING, initiating a response characterized by the production of type I IFNs through the TBK1/IRF3 axis [1, 2]. The helicase DDX41 may play a role in the recognition of c-di-GMP upstream of STING [3].

Recent studies have also demonstrated that c-di-GMP exhibits potent adjuvant properties [4].

References

1. Jin L. et al., 2011. MPYS is required for IFN response factor 3 activation and type I IFN production in the response of cultured phagocytes to bacterial second messengers cyclic-di-AMP and cyclic-di-GMP. J Immunol. 187(5):2595-601.
2. Burdette DL. et al., 2011. STING is a direct innate immune sensor of cyclic di-GMP. Nature. 478(7370):515-8.
3. Parvatiyar K. et al., 2012 The helicase DDX41 recognizes the bacterial secondary messengers cyclic di-GMP and cyclic di-AMP to activate a type I IFN immune response. Nat. Immunol.13(12):1155-61.
4. Madhun AS. et al., 2011. Intranasal c-di-GMP-adjuvanted plant-derived H5 influenza vaccine induces multifunctional Th1 CD4+ cells and strong mucosal and systemic antibody responses in mice. Vaccine.29(31):4973-82.

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 di-guanylate monophosphate, c-di-GMP sodium salt.

CAS number: 2222132-40-1 / 61093-23-0 (free acid).

Formula: C₂₀H₂₂N₁₀O₁₄P₂ .2Na.

Molecular weight: 734.38 g/mol

Purity: ≥ 95% by LC/MS.

Solubility: 50 mg/ml in water.

Quality control:

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

Contents

c-di-GMP is sterile filtered prior to lyophilization.

• 1 mg lyophilized c-di-GMP.
• 1.5 ml endotoxin-free water.

c-di-GMP is shipped at room temperature

Upon receipt it should be stored at -20 °C.

Details

Structure of c-di-GMP