Synthesis of Novel 3’,3’-cyclic Dinucleotide Analogues Targeting STING Protein

0565752 - ÚOCHB 2024 RIV DE eng J - Článek v odborném periodiku
Magand, J. - Roy, V. - Meudal, H. - Rose, S. - Quesniaux, V. - Chalupská, Dominika - Agrofoglio, L. A.
Synthesis of Novel 3’,3’-cyclic Dinucleotide Analogues Targeting STING Protein.
Asian Journal of Organic Chemistry. Roč. 12, č. 1 (2023), č. článku e202200597. ISSN 2193-5807. E-ISSN 2193-5815
Institucionální podpora: RVO:61388963
Klíčová slova: CuAAC * 3’,3’-cyclic dinucleotides * macrocyclization * ring-closing metathesis * STING protein * 1,2,3-triazole
Obor OECD: Organic chemistry
Impakt faktor: 2.7, rok: 2022
Způsob publikování: Open access
https://doi.org/10.1002/ajoc.202200597

The Stimulator of Interferon Genes (STING) plays an important role in innate immunity by inducing type I interferons in response to sensing viral or bacterial cytosolic DNA. Cyclic dinucleotides (CDNs) are known to activate STING. Here, we describe the synthesis and biological evaluation of two new 3’,3’-CDN, in which the internucleotide linkages were replaced, respectively, by a 1,2,3-triazole moiety (as more stable isosteres of phosphate linkers) and an unsaturated carbon chain (as flexibility can led to crucial binding affinity and specificity). Thus, CuAAC and macrocyclization by RCM are the two key steps.
Trvalý link: https://hdl.handle.net/11104/0337260