{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T15:22:43Z","timestamp":1788362563769,"version":"build-2803163510"},"reference-count":31,"publisher":"American Chemical Society (ACS)","issue":"23","license":[{"start":{"date-parts":[[2020,6,3]],"date-time":"2020-06-03T00:00:00Z","timestamp":1591142400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_termsofuse.html"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,6,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The metazoan second messenger 2\u20323\u2032-cyclic guanosine monophosphate\u2013adenosine monophosphate (cGAMP) is a cyclic dinucleotide (CDN) that induces secretion of type I interferons and activates the immune system and has thus attracted significant interest as a vaccine adjuvant or immunotherapeutic. CDN bisphosphorothioates are of particular interest because of their increased hydrolytic stability and improved cell activities. In our work with CDN bisphosphorothioates, we sought a method for systematic determination of the absolute stereochemistry of their phosphorothioate stereocenters. A novel biocatalytic method employing snake venom phosphodiesterase (svPDE) and nP1 has been developed and successfully applied to stereochemistry determination of 2\u20323\u2032-cGAMP bisphosphorothioates. This method unambiguously assigned the phosphorothioate stereochemistry of four diastereomers of 2\u20323\u2032-cGAMP bisphosphorothioate by analyzing distinct hydrolysis patterns of the bisphosphorothioate diastereomers upon incubation with svPDE and nP1. Furthermore, the regiospecificity as well as stereospecificity of both svPDE and nP1 toward 2\u20323\u2032-cGAMP bisphosphorothioate has been elucidated.<\/jats:p>","DOI":"10.1021\/acsomega.0c01942","type":"journal-article","created":{"date-parts":[[2020,6,3]],"date-time":"2020-06-03T13:33:40Z","timestamp":1591191220000},"page":"14173-14179","source":"Crossref","is-referenced-by-count":9,"title":["Novel Applications of Biocatalysis to Stereochemistry\nDetermination of 2\u20323\u2032-cGAMP Bisphosphorothioate (2\u20323\u2032-cGSASMP)"],"prefix":"10.1021","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3402-7810","authenticated-orcid":true,"given":"Jongwon","family":"Lim","sequence":"first","affiliation":[{"name":"Merck & Co., Inc. , , 33 Avenue Louis Pasteur , , ,","place":["Boston, Massachusetts, United States, 02115"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9010-4895","authenticated-orcid":true,"given":"Hai-Young","family":"Kim","sequence":"additional","affiliation":[{"name":"Merck & Co., Inc. , , 33 Avenue Louis Pasteur , , ,","place":["Boston, Massachusetts, United States, 02115"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2020,6,3]]},"reference":[{"key":"2026090211012713300_cit1","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1038\/325279a0","article-title":"Regulation of Cellulose\nSynthesis in Acetobacter Xylinum by Cyclic Diguanylic Acid","volume":"325","author":"Ross","year":"1987","journal-title":"Nature"},{"key":"2026090211012713300_cit2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1128\/MMBR.00043-12","article-title":"Cyclic di\u2013GMP:\nthe First 25\nYears of a Universal Bacterial Second Messenger","volume":"77","author":"Ro\u0308mling","year":"2013","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"2026090211012713300_cit3","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1111\/mmi.13026","article-title":"A Jack of\nAll Trades: the Multiple Roles of the Unique Essential Second Messenger\nCyclic di\u2013AMP","volume":"97","author":"Commichau","year":"2015","journal-title":"Mol. Microbiol."},{"key":"2026090211012713300_cit4","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1126\/science.1232458","article-title":"Cyclic GMP\u2013AMP\nSynthase Is a Cytosolic DNA Sensor that Activates the Type I Interferon\nPathway","volume":"339","author":"Sun","year":"2013","journal-title":"Science"},{"key":"2026090211012713300_cit5","doi-asserted-by":"publisher","first-page":"826","DOI":"10.1126\/science.1229963","article-title":"Cyclic GMP\u2013AMP Is an Endogenous Second Messenger\nin Innate Immune Signaling by Cytosolic DNA","volume":"339","author":"Wu","year":"2013","journal-title":"Science"},{"key":"2026090211012713300_cit6","doi-asserted-by":"publisher","first-page":"1094","DOI":"10.1016\/j.cell.2013.04.046","article-title":"Cyclic [G(2\u2032,5\u2032)pA(3\u2032,5\u2032)p]\nIs the Metazoan Second Messenger Produced by DNA\u2013Activated\nCyclic GMP\u2013AMP Synthase","volume":"153","author":"Gao","year":"2013","journal-title":"Cell"},{"key":"2026090211012713300_cit7","doi-asserted-by":"publisher","first-page":"1355","DOI":"10.1016\/j.celrep.2013.05.009","article-title":"The Innate\nImmune DNA Sensor cGAS Produces a Noncanonical Cyclic Dinucleotide\nthat Activates Human STING","volume":"3","author":"Diner","year":"2013","journal-title":"Cell Rep."},{"key":"2026090211012713300_cit8","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1038\/nature12306","article-title":"cGAS Produces\na 29\u201359\u2013Linked Cyclic Dinucleotide Second Messenger\nthat Activates STING","volume":"498","author":"Ablasser","year":"2013","journal-title":"Nature"},{"key":"2026090211012713300_cit9","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1177\/2051013613501988","article-title":"Rationale, Progress\nand Development of Vaccines Utilizing STING\u2013Activating Cyclic\nDinucleotide Adjuvants","volume":"1","author":"Dubensky","year":"2013","journal-title":"Ther. 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WO Patent WO2014189805, 2014."},{"key":"2026090211012713300_cit13","doi-asserted-by":"publisher","first-page":"10253","DOI":"10.1021\/acs.jmedchem.6b01300","article-title":"Design, Synthesis, and Biological\nEvaluation of Novel Cyclic Adenosine\u2013Inosine Monophosphate\n(cAIMP) Analogs that Activate Stimulator of Interferon Genes (STING)","volume":"59","author":"Lioux","year":"2016","journal-title":"J. Med. Chem."},{"key":"2026090211012713300_cit14","unstructured":"Altman, M. D.; Andresen, B.; Chang, W.; Childers, M. L.; Cumming, J. N.; Haidle, A. M.; Henderson, T. J.; Jewell, J. P.; Liang, R.; Lim, J.; Liu, H.; Lu, M.; Northrup, A. B.; Otte, R. D.; Siu, T.; Trotter, B. W.; Truong, Q. T.; Walsh, S. P.; Zhao, K.\n          Cyclic\nDi\u2013Nucleotide Compounds as STING Agonists.\nWO Patent WO2017027646, 2017."},{"key":"2026090211012713300_cit15","unstructured":"Andresen, B. M.; Bennett, F.; Chang, W.; Childers, M. L.; Cumming, J. N.; Lim, J.; Lu, M.; Trotter, B. 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WO Patent WO2011003025, 2011."},{"key":"2026090211012713300_cit31","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1002\/chir.20905","article-title":"Diastereomerically Pure Nucleoside\u20135\u2032-O-\n(2\u2013thio\u20134,4\u2013pentamethylene\u20131,3,2\u2013oxathiaphospholane)s\u2013Substrates\nfor Synthesis of P\u2013Chiral Derivatives of Nucleoside\u20135\u2032-O-phosphorothioates","volume":"23","author":"Tomaszewska","year":"2011","journal-title":"Chirality"}],"container-title":["ACS Omega"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsomega.0c01942","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/5\/23\/14173\/67810619\/acsomega.0c01942.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/5\/23\/14173\/67810619\/acsomega.0c01942.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T15:01:36Z","timestamp":1788361296000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/acsodf\/article\/5\/23\/14173\/504470\/Novel-Applications-of-Biocatalysis-to"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,3]]},"references-count":31,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2020,6,3]]},"published-print":{"date-parts":[[2020,6,16]]}},"URL":"https:\/\/doi.org\/10.1021\/acsomega.0c01942","relation":{},"ISSN":["2470-1343"],"issn-type":[{"value":"2470-1343","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,3]]}}}