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

0565752 - ÚOCHB 2024 RIV DE eng J - Journal Article
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
Institutional support: RVO:61388963
Keywords : CuAAC * 3’,3’-cyclic dinucleotides * macrocyclization * ring-closing metathesis * STING protein * 1,2,3-triazole
OECD category: Organic chemistry
Impact factor: 2.7, year: 2022
Method of publishing: 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.
Permanent Link: https://hdl.handle.net/11104/0337260