Tuning the Innate Immune Response to Cyclic Dinucleotides by Using Atomic Mutagenesis.
STING agonists
cyclic dinucleotides
innate immune response
modified nucleosides
Journal
Chembiochem : a European journal of chemical biology
ISSN: 1439-7633
Titre abrégé: Chembiochem
Pays: Germany
ID NLM: 100937360
Informations de publication
Date de publication:
14 09 2020
14 09 2020
Historique:
received:
15
03
2020
revised:
24
04
2020
pubmed:
30
4
2020
medline:
8
7
2021
entrez:
30
4
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32346955
doi: 10.1002/cbic.202000162
pmc: PMC7494572
mid: NIHMS1595579
doi:
Substances chimiques
Nucleotides, Cyclic
0
Interferons
9008-11-1
Cyclic GMP
H2D2X058MU
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2595-2598Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM069773
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM124589
Pays : United States
Informations de copyright
© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
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