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Novel Applications of Biocatalysis to Stereochemistry Determination of 2′3′-cGAMP Bisphosphorothioate (2′3′-cG(S)A(S)MP)
[Image: see text] The metazoan second messenger 2′3′-cyclic guanosine monophosphate–adenosine 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 immunot...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301576/ https://www.ncbi.nlm.nih.gov/pubmed/32566885 http://dx.doi.org/10.1021/acsomega.0c01942 |
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author | Lim, Jongwon Kim, Hai-Young |
author_facet | Lim, Jongwon Kim, Hai-Young |
author_sort | Lim, Jongwon |
collection | PubMed |
description | [Image: see text] The metazoan second messenger 2′3′-cyclic guanosine monophosphate–adenosine 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′3′-cGAMP bisphosphorothioates. This method unambiguously assigned the phosphorothioate stereochemistry of four diastereomers of 2′3′-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′3′-cGAMP bisphosphorothioate has been elucidated. |
format | Online Article Text |
id | pubmed-7301576 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-73015762020-06-19 Novel Applications of Biocatalysis to Stereochemistry Determination of 2′3′-cGAMP Bisphosphorothioate (2′3′-cG(S)A(S)MP) Lim, Jongwon Kim, Hai-Young ACS Omega [Image: see text] The metazoan second messenger 2′3′-cyclic guanosine monophosphate–adenosine 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′3′-cGAMP bisphosphorothioates. This method unambiguously assigned the phosphorothioate stereochemistry of four diastereomers of 2′3′-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′3′-cGAMP bisphosphorothioate has been elucidated. American Chemical Society 2020-06-03 /pmc/articles/PMC7301576/ /pubmed/32566885 http://dx.doi.org/10.1021/acsomega.0c01942 Text en Copyright © 2020 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes. |
spellingShingle | Lim, Jongwon Kim, Hai-Young Novel Applications of Biocatalysis to Stereochemistry Determination of 2′3′-cGAMP Bisphosphorothioate (2′3′-cG(S)A(S)MP) |
title | Novel Applications of Biocatalysis to Stereochemistry
Determination of 2′3′-cGAMP Bisphosphorothioate (2′3′-cG(S)A(S)MP) |
title_full | Novel Applications of Biocatalysis to Stereochemistry
Determination of 2′3′-cGAMP Bisphosphorothioate (2′3′-cG(S)A(S)MP) |
title_fullStr | Novel Applications of Biocatalysis to Stereochemistry
Determination of 2′3′-cGAMP Bisphosphorothioate (2′3′-cG(S)A(S)MP) |
title_full_unstemmed | Novel Applications of Biocatalysis to Stereochemistry
Determination of 2′3′-cGAMP Bisphosphorothioate (2′3′-cG(S)A(S)MP) |
title_short | Novel Applications of Biocatalysis to Stereochemistry
Determination of 2′3′-cGAMP Bisphosphorothioate (2′3′-cG(S)A(S)MP) |
title_sort | novel applications of biocatalysis to stereochemistry
determination of 2′3′-cgamp bisphosphorothioate (2′3′-cg(s)a(s)mp) |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301576/ https://www.ncbi.nlm.nih.gov/pubmed/32566885 http://dx.doi.org/10.1021/acsomega.0c01942 |
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