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 und Carell, Thomas (10. Dezember 2018): A Click-Chemistry Linked 2’3’-cGAMP Analog. In: Chemistry-A European Journal, Bd. 25: S. 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.

• Dokumententyp: Zeitschriftenartikel
• EU Funded Grant Agreement Number: 741912
• EU-Projekte: Horizon 2020 > ERC Grants > ERC Advanced Grant > ERC Grant 741912: EPiR - The Chemical Basis of RNA Epigenetics
• Publikationsform: Postprint
• Keywords: cGAMP analog; cGAS; STING; ENPP1; cyclophane; CuAAC; macrolactamization
• Fakultät: Chemie und Pharmazie ; Chemie und Pharmazie > Department Chemie
• Fakultätsübergreifende Einrichtungen: Center for Integrated Protein Science Munich (CIPSM)
• Themengebiete: 500 Naturwissenschaften und Mathematik > 540 Chemie
• ISSN: 0947-6539
• Sprache: Englisch