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Updated: Jun 22, 2026
12:31
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.
Chemistry (Weinheim an Der Bergstrasse, Germany)
|December 12, 2018
Summary
Researchers synthesized a novel cyclic GMP-AMP (cGAMP) analog with improved cell penetration. This new molecule features amide and triazole linkages, offering potential for enhanced innate immunity activation via the STING pathway.
Area of Science:
- Biochemistry
- Immunology
- Organic Chemistry
Background:
- 2'3'-cGAMP is a cyclic dinucleotide produced by cGAS in response to cytosolic DNA.
- cGAMP activates the STING pathway, a crucial component of innate immunity.
- There is a need for cGAMP analogs with uncharged linkages for better cellular penetration.
Purpose of the Study:
- To synthesize a novel cGAMP analogue with improved cellular penetrability.
- To explore the use of amide and triazole linkages in cGAMP analogue design.
- To develop efficient synthetic routes for these modified cyclic dinucleotides.
Main Methods:
- Cu(I)-catalyzed click chemistry to form the triazole linkage.
- Macrolactamization for cyclization to form the analogue.
- Characterization of the synthesized cGAMP analogue.
Main Results:
- Successful synthesis of a cGAMP analogue incorporating one amide and one triazole linkage.
- The synthetic strategy efficiently established the desired linkages.
- The resulting analogue is expected to exhibit enhanced cellular penetration.
Conclusions:
- The developed synthetic methodology provides access to novel cGAMP analogues.
- These analogues hold promise for modulating innate immunity through the STING pathway.
- The design offers a potential strategy for developing more effective immunomodulatory agents.
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