A Click-Chemistry Linked 2′3′-cGAMP Analogue

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

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

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

Original languageEnglish
Pages (from-to)2089-2095
Number of pages7
JournalChemistry - A European Journal
Volume25
Issue number8
DOIs
Publication statusPublished - 2019 Feb 6
Externally publishedYes

Keywords

  • STING
  • cGAMP analogue
  • click chemistry
  • cyclophane
  • macrolactamization

ASJC Scopus subject areas

  • Catalysis
  • Organic Chemistry

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