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Updated: Jun 22, 2026

Chemoselective Modification of Viral Surfaces via Bioorthogonal Click Chemistry
Published on: August 19, 2012
A Click-Chemistry Linked 2'3'-cGAMP Analogue
Clemens Reto Dialer1, Samuele Stazzoni1, David Jan Drexler2
1Department of Chemistry, Ludwig-Maximilians-Universität München, Butenandtstrasse 5-13, 81377, Munich, Germany.
Abstract:
2'3'-cGAMP is an uncanonical cyclic dinucleotide where one A and one G base are connected via a 3'-5' and a unique 2'-5' linkage. The molecule is produced by the cyclase cGAS in response to cytosolic DNA binding. cGAMP activates STING and hence one of the most powerful pathways of innate immunity. cGAMP analogues with uncharged linkages that feature better cellular penetrability are currently highly desired. Here, the synthesis of a cGAMP analogue with one amide and one triazole linkage is reported. The molecule is best prepared via a first CuI -catalyzed click reaction, which establishes the triazole, while the cyclization is achieved by macrolactamization.
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