New Assay for Immunology Research Quantifies cGAS-Produced 2’3’-cGAMP in Cells
Ann Arbor, MI, July 20, 2018 --(PR.com)-- Sensitive and direct measurement of cGAMP levels in cell lysates is now possible with Cayman’s much-anticipated 2’3’-cGAMP ELISA Kit. Developed by Cayman scientists, in conjunction with expert nucleotide scientists at Biolog Life Science Institute in Germany, this competitive assay offers key improvements from the previous methods used to quantify 2’3’-cGAMP content. The assay has a large detection range (100 ng/ml – 6.1 pg/ml), an excellent Lower Limit of Detection (LLOD = 9.6 pg/ml), and cross reactivity from related cyclic dinucleotides is essentially absent.
2’3’-cGAMP acts as a second messenger during host defense and may also have roles in autoimmune or inflammatory diseases, including cancer. It is produced when the DNA sensor, cyclic GMP-AMP synthase (cGAS), detects the presence of nucleic acids in the cytosol of mammalian cells as an indicator of bacterial or viral infection. Self-nucleic acids (RNA and DNA) or damaged nucleic acids can also trigger cGAS to produce 2’3’-cGAMP, which binds tightly to the adaptor protein STING (stimulator of interferon genes). This initiates the recruitment and activation of downstream proteins (TBK1 and IRF3) that induce the transcription and translation of type I interferon, a potent anti-viral cytokine. Modulation of cGAS activity with subsequent induction or inhibition of 2’3’-cGAMP formation is an active target of pharmacological intervention for cancer immunotherapies and autoimmune therapies. By enabling sensitive, accurate quantification of cGAMP levels in cells, Cayman’s 2’3’-cGAMP ELISA Kit can be used to assess the effectiveness of novel inhibitors in preclinical studies.
“We are delighted about the successful collaboration in developing this 2’3’-cGAMP ELISA Kit as an important next generation tool to detect the second messenger 2’3’-cGAMP at an unprecedented sensitivity in the low pg/ml range,” states Frank Schwede, Ph.D., the head of research and development at Biolog Life Science Institute. “Indeed, unrivaled sensitivity of this ELISA is its key feature,” notes Jim Mobley, Ph.D., the director of Cayman’s new product development. “The ELISA is a more cost-effective option than mass spectrometry, and significantly more sensitive than a recently published fluorescence polarization assay.1 This ELISA should be a boon to anyone looking to identify compounds that modulate cGAS activity by measuring cGAMP formation.” The assay is also a breakthrough for nonclinical users needing quantify 2’3’-cGAMP content, since the assay is highly suitable for monitoring the kinetics of 2’3’-cGAMP formation and hydrolysis in a biological setting.
This assay kit fits within a suite of tools available from Cayman to study the cGAS-STING-IFN signaling axis. A Cayman Currents issue on Innate Immune Signaling: cGAS/STING is available to learn more about the cyclic dinucleotides, 2’2’-, 2’3’-, and 3’3’-cGAMPs, recombinant STING variants, and additional key proteins and antibodies to study this area of therapeutic interest.
1. Hall, J., Brault, A., Vincent, F., et al. Discovery of PF-06928215 as a high affinity inhibitor of cGAS enabled by novel fluorescence polarization assay. PLoS ONE 12(9), e0184843 (2017).
About Cayman Chemical Company
Cayman Chemical Company helps make research possible by supplying scientists worldwide with biochemical tools used to understand immunology, inflammation, cancer, neurochemistry, oxidative injury, endocrinology, atherosclerosis, and other human health challenges. Our scientists are experts in the synthesis, purification, and characterization of biochemicals ranging from small drug-like heterocycles to complex biolipids, fatty acids, and many others for use as research reagents and qualified standards. We are also highly skilled in all aspects of assay and antibody development, protein expression, crystallization, and structure determination. In addition, we offer a wide range of analytical services using LC-MS/MS, HPLC, GC, and many other techniques. Cayman performs generic drug development and production in both Ann Arbor, Michigan and Neratovice, Czech Republic.
About Biolog Life Science Institute
Biolog Life Science Institute is an innovative and science-driven enterprise based in Germany which specializes in tools for signal transduction research. The ISO 9001-certified company has its focus on nucleotide chemistry with a special emphasis on cyclic dinucleotide and cyclic nucleotide analogs of the second messengers 2’3’-cGAMP, c-diGMP, c-diAMP, cAMP, and cGMP. Biolog is the leading supplier of specialized triphosphates, Epac-related products, and NAD+/cADPR analogs. A strong scientific expertise and collaborations with leading researchers foster the continual release of new, unique products, including a wide range of fluorescent and biotinylated nucleotide analogs.
2’3’-cGAMP acts as a second messenger during host defense and may also have roles in autoimmune or inflammatory diseases, including cancer. It is produced when the DNA sensor, cyclic GMP-AMP synthase (cGAS), detects the presence of nucleic acids in the cytosol of mammalian cells as an indicator of bacterial or viral infection. Self-nucleic acids (RNA and DNA) or damaged nucleic acids can also trigger cGAS to produce 2’3’-cGAMP, which binds tightly to the adaptor protein STING (stimulator of interferon genes). This initiates the recruitment and activation of downstream proteins (TBK1 and IRF3) that induce the transcription and translation of type I interferon, a potent anti-viral cytokine. Modulation of cGAS activity with subsequent induction or inhibition of 2’3’-cGAMP formation is an active target of pharmacological intervention for cancer immunotherapies and autoimmune therapies. By enabling sensitive, accurate quantification of cGAMP levels in cells, Cayman’s 2’3’-cGAMP ELISA Kit can be used to assess the effectiveness of novel inhibitors in preclinical studies.
“We are delighted about the successful collaboration in developing this 2’3’-cGAMP ELISA Kit as an important next generation tool to detect the second messenger 2’3’-cGAMP at an unprecedented sensitivity in the low pg/ml range,” states Frank Schwede, Ph.D., the head of research and development at Biolog Life Science Institute. “Indeed, unrivaled sensitivity of this ELISA is its key feature,” notes Jim Mobley, Ph.D., the director of Cayman’s new product development. “The ELISA is a more cost-effective option than mass spectrometry, and significantly more sensitive than a recently published fluorescence polarization assay.1 This ELISA should be a boon to anyone looking to identify compounds that modulate cGAS activity by measuring cGAMP formation.” The assay is also a breakthrough for nonclinical users needing quantify 2’3’-cGAMP content, since the assay is highly suitable for monitoring the kinetics of 2’3’-cGAMP formation and hydrolysis in a biological setting.
This assay kit fits within a suite of tools available from Cayman to study the cGAS-STING-IFN signaling axis. A Cayman Currents issue on Innate Immune Signaling: cGAS/STING is available to learn more about the cyclic dinucleotides, 2’2’-, 2’3’-, and 3’3’-cGAMPs, recombinant STING variants, and additional key proteins and antibodies to study this area of therapeutic interest.
1. Hall, J., Brault, A., Vincent, F., et al. Discovery of PF-06928215 as a high affinity inhibitor of cGAS enabled by novel fluorescence polarization assay. PLoS ONE 12(9), e0184843 (2017).
About Cayman Chemical Company
Cayman Chemical Company helps make research possible by supplying scientists worldwide with biochemical tools used to understand immunology, inflammation, cancer, neurochemistry, oxidative injury, endocrinology, atherosclerosis, and other human health challenges. Our scientists are experts in the synthesis, purification, and characterization of biochemicals ranging from small drug-like heterocycles to complex biolipids, fatty acids, and many others for use as research reagents and qualified standards. We are also highly skilled in all aspects of assay and antibody development, protein expression, crystallization, and structure determination. In addition, we offer a wide range of analytical services using LC-MS/MS, HPLC, GC, and many other techniques. Cayman performs generic drug development and production in both Ann Arbor, Michigan and Neratovice, Czech Republic.
About Biolog Life Science Institute
Biolog Life Science Institute is an innovative and science-driven enterprise based in Germany which specializes in tools for signal transduction research. The ISO 9001-certified company has its focus on nucleotide chemistry with a special emphasis on cyclic dinucleotide and cyclic nucleotide analogs of the second messengers 2’3’-cGAMP, c-diGMP, c-diAMP, cAMP, and cGMP. Biolog is the leading supplier of specialized triphosphates, Epac-related products, and NAD+/cADPR analogs. A strong scientific expertise and collaborations with leading researchers foster the continual release of new, unique products, including a wide range of fluorescent and biotinylated nucleotide analogs.
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Cayman Chemical Company
Jason Truskowski
(734) 975-3897
www.caymanchem.com
Jason Truskowski
(734) 975-3897
www.caymanchem.com
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