A Click-Chemistry Linked 2’3’-cGAMP Analog

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 (10. December 2018): A Click-Chemistry Linked 2’3’-cGAMP Analog. In: Chemistry-A European Journal, Vol. 25: pp. 2089-2095

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 analogs with uncharged linkages that feature better cellular penetrability are currently highly desired. Here, we report the synthesis of a cGAMP analog with one amide and one triazole linkage. The molecule is best prepared via a first Cu(I) catalysed click reaction which establishes the triazole, while the cyclization is achieved by macrolactamization.

• Item Type: Journal article
• EU Funded Grant Agreement Number: 741912
• EU Projects: Horizon 2020 > ERC Grants > ERC Advanced Grant > ERC Grant 741912: EPiR - The Chemical Basis of RNA Epigenetics
• Form of publication: Postprint
• Keywords: cGAMP analog; cGAS; STING; ENPP1; cyclophane; CuAAC; macrolactamization
• Faculties: Chemistry and Pharmacy; Chemistry and Pharmacy > Department of Chemistry
• Research Centers: Center for Integrated Protein Science Munich (CIPSM)
• Subjects: 500 Science > 540 Chemistry
• ISSN: 0947-6539
• Language: English