Catalytic promiscuity of cGAS: a facile enzymatic synthesis of 2′-3′-Linked cyclic dinucleotides
| dc.contributor.author | Rosenthal, Katrin | |
| dc.contributor.author | Becker, Martin | |
| dc.contributor.author | Rolf, Jascha | |
| dc.contributor.author | Siedentop, Regine | |
| dc.contributor.author | Hillen, Michael | |
| dc.contributor.author | Nett, Markus | |
| dc.contributor.author | Lütz, Stephan | |
| dc.date.accessioned | 2021-07-19T11:34:34Z | |
| dc.date.available | 2021-07-19T11:34:34Z | |
| dc.date.issued | 2020-07-07 | |
| dc.description.abstract | Enzymatic shortcut: Cyclic dinucleotides, which are of great interest to study immunology and immune oncology, can be synthesized in a one-step biotransformation significantly shortening the chemical synthesis route. The enzyme displays a surprisingly large substrate scope. Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor that catalyzes the synthesis of the cyclic GMP-AMP dinucleotide 2′3′-cGAMP. 2′3′-cGAMP functions as inducer for the production of type I interferons. Derivatives of this important second messenger are highly valuable for pharmaceutical applications. However, the production of these analogues requires complex, multistep syntheses. Herein, human cGAS is shown to react with a series of unnatural nucleotides, thus leading to novel cyclic dinucleotides. Most substrate derivatives with modifications at the nucleobase, ribose, and the α-thio phosphate were accepted. These results demonstrate the catalytic promiscuity of human cGAS and its utility for the biocatalytic synthesis of cyclic dinucleotide derivatives. | en |
| dc.identifier.uri | http://hdl.handle.net/2003/40333 | |
| dc.identifier.uri | http://dx.doi.org/10.17877/DE290R-22208 | |
| dc.language.iso | en | de |
| dc.relation.ispartofseries | ChemBioChem;Vol. 21. 2020, Issue 22, pp 3225-3228 | |
| dc.relation.uri | https://creativecommons.org/licenses/by/4.0/ | |
| dc.subject | biocatalysis | en |
| dc.subject | catalytic promiscuity | en |
| dc.subject | cGAS | en |
| dc.subject | Cyclic dinucleotides | en |
| dc.subject | Enzymes | en |
| dc.subject.ddc | 660 | |
| dc.title | Catalytic promiscuity of cGAS: a facile enzymatic synthesis of 2′-3′-Linked cyclic dinucleotides | en |
| dc.type | Text | de |
| dc.type.publicationtype | article | de |
| dcterms.accessRights | open access | |
| eldorado.secondarypublication | true | de |
| eldorado.secondarypublication.primarycitation | ChemBioChem. Vol. 21. 2020, Issue 22, pp 3225-3228 | de |
| eldorado.secondarypublication.primaryidentifier | https://doi.org/10.1002/cbic.202000433 | de |