A click-chemistry linked 2'3'-cGAMP analogue

December 10, 2018

Dialer, Clemens Reto, Samuele Stazzoni, David Jan Drexler, Felix Moritz Müller, Simon Veth, Alexander Pichler, Hidenori Okamura, Gregor Witte, Karl‐Peter Hopfner, and Thomas Carell

Chemistry 2019 Feb 6;25(8):2089-2095. doi: 10.1002/chem.201805409

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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Topics: Tycho, Proteins, Publications

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