A Click-Chemistry Linked 2′3′-cGAMP Analogue |
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Authors: | Clemens Reto Dialer Samuele Stazzoni David Jan Drexler Felix Moritz Müller Simon Veth Alexander Pichler Dr Hidenori Okamura Dr Gregor Witte Prof?Dr Karl-Peter Hopfner Prof?Dr Thomas Carell |
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Institution: | 1. Department of Chemistry, Ludwig-Maximilians-Universität München, Butenandtstrasse 5–13, 81377 Munich, Germany;2. Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität München, Feodor-Lynen-Strasse 25, 81377 Munich, Germany |
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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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Keywords: | cGAMP analogue click chemistry cyclophane macrolactamization STING |
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