Design, Synthesis, and Biochemical and Biological Evaluation of Novel 7-Deazapurine Cyclic Dinucleotide Analogues as STING Receptor Agonists
Zdeněk Vavřina, Pavla Perlíková, Nemanja Milisavljevič, Florian Chevrier, Miroslav Smola, Joshua Smith, Milan Dejmek, Vojtěch Havlíček, Miloš Buděšı́nský, Radek Liboska, Lenka Vaneková, J. Brynda, Evžen Bouřa, Pavlína Řezáčová, Michal Hocek, Gabriel Birkuš
Abstract
GAMP, the natural ligand of STING. The effect on cytokine and chemokine induction was also evaluated. The best activities were observed for CDNs bearing large aromatic substituents that point above the CDN molecule. We solved four X-ray structures of complexes of new CDNs with human STING. We observed π-π stacking interactions between the aromatic substituents and Tyr240 that are involved in the stabilization of CDN-STING complexes.
Topics & Concepts
ChemistryStimulator of interferon genesStingLigand (biochemistry)StackingStereochemistryMoietyCombinatorial chemistryReceptorBiochemistryInnate immune systemOrganic chemistryEngineeringAerospace engineeringinterferon and immune responsesViral Infections and VectorsHerpesvirus Infections and Treatments