A Click-Chemistry Linked 23-cGAMP Analogue

被引：14

作者：

Dialer, Clemens Reto ^{[1
]}

Stazzoni, Samuele ^{[1
]}

Drexler, David Jan ^{[2
,3
]}

Mueller, Felix Moritz ^{[1
]}

Veth, Simon ^{[1
]}

Pichler, Alexander ^{[1
]}

Okamura, Hidenori ^{[1
]}

Witte, Gregor ^{[2
,3
]}

Hopfner, Karl-Peter ^{[2
,3
]}

Carell, Thomas ^{[1
]}

机构：

[1] Ludwig Maximilians Univ Munchen, Dept Chem, Butenandtstr 5-13, D-81377 Munich, Germany

[2] Ludwig Maximilians Univ Munchen, Gene Ctr, Feodor Lynen Str 25, D-81377 Munich, Germany

[3] Ludwig Maximilians Univ Munchen, Dept Biochem, Feodor Lynen Str 25, D-81377 Munich, Germany

来源：

CHEMISTRY-A EUROPEAN JOURNAL | 2019年 / 25卷 / 08期

基金：

欧洲研究理事会;

关键词：

cGAMP analogue; click chemistry; cyclophane; macrolactamization; STING; C-DI-GMP; STING PATHWAY; ENDOGENOUS; 2ND-MESSENGER; CYCLIC DINUCLEOTIDES; EFFICIENT SYNTHESIS; AMP; DESIGN; MECHANISM;

D O I：

10.1002/chem.201805409

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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.

引用

页码：2089 / 2095

页数：7

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