2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO
生物活性
Description
In Vivo
In Vitro
化合物的使用
Kinase Assay
Cell Assay
Animal Administration
参考文献
Cyclic di-AMP (also called c-di-AMP and c-di-adenosine monophosphate) is a second messenger used in signal transduction in bacteria.It is present in many Gram-positive bacteria, some Gram-negative species, and possibly some archaea.
It is one of many ubiquitous nucleotide second messengers including cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), guanosine pentaphosphate ((p)ppGpp), and cyclic di-GMP (c-di-GMP). c-di-AMP is a signaling nucleotide used in signaling pathways that trigger outputs by using receptor or target proteins to sense c-di-AMP concentrations in the cell.
In bacteria, cyclic di-AMP has been implicated in the control of growth, cell wall homeostasis, bacterial biofilm formation and virulence gene expression, heat and osmotic stress regulation and responses, sporulation, potassium transport, lysis, and antibiotic resistance.
In humans, cyclic di-AMP has been implicated in the control of innate immune response and antiviral response against pathogens. The dinucleotide is also produced by numerous human pathogens, prompting the exploration of numerous c-di-AMP-regulating pathways both in humans and in bacteria.
Phosphodiesterase (PDE) enzymes degrade cyclic di-AMP to the linear molecule 5’-pApA (phosphadenylyl adenosine). pApA is also involved in a feedback inhibition loop that limits GdpP gene-dependent c-di-AMP hydrolysis, leading to elevated c-di-AMP levels.
It is suggested that cyclic di-AMP is involved in the regulation of cell lysis. Studies have shown that bacterial mutant strains with low c-di-AMP levels lysed significantly faster than their parent strains.
Cyclic di-AMP has also been linked to bacterial RNA synthesis inhibition. c-di-AMP stimulates the production of (p)ppGpp, an alarmone involved in bacterial stringent response.
In eukaryotic cells, c-di-AMP is sensed and subsequently elicits a type I interferon (IFN) response, leading to the activation of defense mechanisms against viral infection. This detection and activation pathway involves STING, TBK1, and IRF3. c-di-AMP may also stimulate dendritic cells, leading to T cell activation.
c-di-AMP activates the innate immune pathway STING (stimulator of interferon genes) to detect damaged DNA. The nucleotide either binds to the helicase DDX41, which in turn activates the STING pathway, or directly binds to the STING protein.Cyclic di-AMP has been identified (along with 2’3’-cGAMP) as a ligand that induces closing of the STING dimer, leading to STING polymerization and pathway activation.When a type I IFN response is not induced in response to c-di-AMP, STING is unable to relocate from the endoplasmic reticulum to the cytoplasm for pathway activation, suggesting that c-di-AMP is a predominant ligand in STING polymerization, and thus activation, via intracellular translocation.
