A Click-Chemistry Linked 23-cGAMP Analogue

Dialer, Clemens Reto; Stazzoni, Samuele; Drexler, David Jan; Müller, Felix Moritz; Veth, Simon; Pichler, Alexander; Okamura, Hidenori; Witte, Gregor; Hopfner, Karl-Peter and Carell, Thomas (2019): A Click-Chemistry Linked 23-cGAMP Analogue. In: Chemistry-A European Journal, Vol. 25, No. 8: pp. 2089-2095

Abstract

23-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 Cu-I-catalyzed click reaction, which establishes the triazole, while the cyclization is achieved by macrolactamization.

• Item Type: Journal article
• Faculties: Chemistry and Pharmacy > Department of Chemistry
• Subjects: 500 Science > 540 Chemistry
• ISSN: 0947-6539
• Language: English