ArticleAnalytical and bioanalytical chemistry2021
Mass spectrometric characterization of cyclic dinucleotides (CDNs) in vivo.
Article in Analytical and bioanalytical chemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 9 citations in OpenAlex.
- Mechanistic reprogramming of the mtDNA-cGAS-STING axis in cellular senescence: from mitochondrial homeostatic disruption to inflammatory and immune outcomes.Biogerontology · 2026Review
- Loss of killifish cGAS attenuates age-related signatures but does not affect organismal life span.EMBO reports · 2026Article
- Mechanistic insights and therapeutic potential of targeting the cGAS-STING pathway in neurodegenerative diseases.Journal of neuroinflammation · 2026Review
- Influence of the Heme Nitric Oxide/Oxygen Binding Protein (H-NOX) on Cell Cycle Regulation in Caulobacter crescentus.Molecular & cellular proteomics : MCP · 2023Article
- The virus-induced cyclic dinucleotide 2'3'-c-di-GMP mediates STING-dependent antiviral immunity in Drosophila.Immunity · 2023Article
- At the Crossroad of Nucleotide Dynamics and Protein Synthesis in Bacteria.Microbiology and molecular biology reviews : MMBR · 2023Review
- Targeting STING: From antiviral immunity to treat osteoporosis.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cyclic dinucleotides (CDNs) are key secondary messenger molecules produced by cyclic dinucleotide synthases that trigger various cellular signaling cascades from bacteria to vertebrates. In mammals, cyclic GMP-AMP synthase (cGAS) has been shown to bind to intracellular DNA and catalyze the production of the dinucleotide 2'3' cGAMP, which signals downstream effectors to regulate immune function, interferon signaling, and the antiviral response. Despite the importance of CDNs, sensitive and accurate methods to measure their levels in vivo are lacking. Here, we report a novel LC-MS/MS method to quantify CDNs in vivo. We characterized the mass spectrometric behavior of four different biologically relevant CDNs (c-di-AMP, c-di-GMP, 3'3' cGAMP, 2'3' cGAMP) and provided a means of visually representing fragmentation resulting from collision-induced dissociation at different energies using collision energy breakdown graphs. We then validated the method and quantified CDNs in two in vivo systems, the bacteria Escherichia coli OP50 and the killifish Nothobranchius furzeri. We found that optimization of LC-MS/MS parameters is crucial to sensitivity and accuracy. These technical advances should help illuminate physiological and pathological roles of these CDNs in in vivo settings. Graphical abstract.
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