Tuning the Innate Immune Response to Cyclic Dinucleotides by Using Atomic Mutagenesis.

Autor: Li Y; Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093-0358, USA., Fin A; Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093-0358, USA., Rovira AR; Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093-0358, USA., Su Y; Department of Chemistry and Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA., Dippel AB; Department of Chemistry and Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA., Valderrama JA; Collaborative to Halt Antibiotic-Resistant Microbes, Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093-0760, USA., Riestra AM; Collaborative to Halt Antibiotic-Resistant Microbes, Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093-0760, USA., Nizet V; Collaborative to Halt Antibiotic-Resistant Microbes, Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093-0760, USA.; Skaggs School of Pharmacy & Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093-0760, USA., Hammond MC; Department of Chemistry and Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.; Department of Chemistry and Henry Eyring Center for Cell and Genome Sciences, University of Utah, Salt Lake City, UT 84112, USA., Tor Y; Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093-0358, USA.
Jazyk: angličtina
Zdroj: Chembiochem : a European journal of chemical biology [Chembiochem] 2020 Sep 14; Vol. 21 (18), pp. 2595-2598. Date of Electronic Publication: 2020 Jun 08.
DOI: 10.1002/cbic.202000162
Abstrakt: Cyclic dinucleotides (CDNs) trigger the innate immune response in eukaryotic cells through the stimulator of interferon genes (STING) signaling pathway. To decipher this complex cellular process, a better correlation between structure and downstream function is required. Herein, we report the design and immunostimulatory effect of a novel group of c-di-GMP analogues. By employing an "atomic mutagenesis" strategy, changing one atom at a time, a class of gradually modified CDNs was prepared. These c-di-GMP analogues induce type-I interferon (IFN) production, with some being more potent than c-di-GMP, their native archetype. This study demonstrates that CDN analogues bearing modified nucleobases are able to tune the innate immune response in eukaryotic cells.
(© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)
Databáze: MEDLINE
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