Novel Poxin Stable cGAMP-Derivatives Are Remarkable STING Agonists.
Antiviral Compound
Immuno Oncology
Poxins
STING
cGAMP
Journal
Angewandte Chemie (International ed. in English)
ISSN: 1521-3773
Titre abrégé: Angew Chem Int Ed Engl
Pays: Germany
ID NLM: 0370543
Informations de publication
Date de publication:
04 10 2022
04 10 2022
Historique:
received:
16
05
2022
pubmed:
26
7
2022
medline:
28
9
2022
entrez:
25
7
2022
Statut:
ppublish
Résumé
2',3'-cGAMP is a cyclic A- and G-containing dinucleotide second messenger, which is formed upon cellular recognition of foreign cytosolic DNA as part of the innate immune response. The molecule binds to the adaptor protein STING, which induces an immune response characterized by the production of type I interferons and cytokines. The development of STING-binding molecules with both agonistic as well as antagonistic properties is currently of tremendous interest to induce or enhance antitumor or antiviral immunity on the one hand, or to treat autoimmune diseases on the other hand. To escape the host innate immune recognition, some viruses encode poxin endonucleases that cleave 2',3'-cGAMP. Here we report that dideoxy-2',3'-cGAMP (1) and analogs thereof, which lack the secondary ribose-OH groups, form a group of poxin-stable STING agonists. Despite their reduced affinity to STING, particularly the compound constructed from two A nucleosides, dideoxy-2',3'-cAAMP (2), features an unusually high antitumor response in mice.
Identifiants
pubmed: 35876840
doi: 10.1002/anie.202207175
pmc: PMC9804856
doi:
Substances chimiques
Antiviral Agents
0
Cytokines
0
Interferon Type I
0
Membrane Proteins
0
Nucleosides
0
Nucleotides, Cyclic
0
Sting1 protein, mouse
0
cyclic guanosine monophosphate-adenosine monophosphate
0
Ribose
681HV46001
DNA
9007-49-2
Nucleotidyltransferases
EC 2.7.7.-
Endonucleases
EC 3.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e202207175Informations de copyright
© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.
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