Issue 4, 2023

10th anniversary of discovering cGAMP: synthesis and beyond

Abstract

The discovery of cGAMP in 2012 filled an important gap in our understanding of innate immune signaling. It has been known for over a century that DNA can induce immune responses, but the underlying mechanism was not clear. With the identification of STING as a key player in interferon induction, the DNA detector that activates STING was the last missing link in TBK1-IRF3 signaling. Somewhat unexpectedly, it turns out that nature relays the DNA danger signal through a small molecule. cGAMP is a cyclic dinucleotide produced from cyclodimerization of ATP and GTP upon detection of cytosolic DNA by cGAS, a previously uncharacterized protein, to promote the assembly of the STING signalosome. This article covers a personal account of the discovery of cGAMP, a short history of the relevant nucleotide chemistry, and a summary of the latest development in this field of research in chemistry. It is the author's hope that, with a historic perspective, the readers can better appreciate the synergy between chemistry and biology in drug development.

Graphical abstract: 10th anniversary of discovering cGAMP: synthesis and beyond

Article information

Article type
Review Article
Submitted
25 दिसम्बर 2022
Accepted
19 जनवरी 2023
First published
25 जनवरी 2023

Org. Chem. Front., 2023,10, 1086-1098

10th anniversary of discovering cGAMP: synthesis and beyond

C. Chen, Org. Chem. Front., 2023, 10, 1086 DOI: 10.1039/D2QO02033E

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements