Catalytic promiscuity of cGAS: A facile enzymatic synthesis of 2'-3' linked cyclic dinucleotides.

Catalytic promiscuity of cGAS: A facile enzymatic synthesis of 2'-3' linked cyclic dinucleotides. Chembiochem. 2020 Jul 07;: Authors: Rosenthal K, Becker M, Rolf J, Siedentop R, Hillen M, Nett M, Lütz S Abstract Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor that catalyzes the synthesis of 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 analogs requires complex, multistep synthesis. Herein, human cGAS is shown to react with a series of non-natural nucleotides, thus leading to novel cyclic dinucleotides. Most substrate derivatives were accepted with modifications at the nucleobase, ribose, as well as the α-thio phosphate. The presented results demonstrate the catalytic promiscuity of human cGAS and its utility for the biocatalytic synthesis of cyclic dinucleotide derivatives. PMID: 32633874 [PubMed - as supplied by publisher]
Source: Chembiochem - Category: Biochemistry Authors: Tags: Chembiochem Source Type: research
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