Affinity selection of double-click triazole libraries for rapid discovery of allosteric modulators for GLP-1 receptor.
- Journal:
- Proceedings of the National Academy of Sciences of the United States of America
- Published:
- DOI:
- 10.1073/pnas.2220767120
- Affiliations:
- 7
- Authors:
- 12
Research Highlight
Double-clicking on novel drug leads
© Andrew Brookes/Image Source/Getty Images
Several promising drug leads have been identified using a high-throughput method for testing large libraries of molecules made using ‘double-click’ chemistry.
Click reactions are highly dependable chemical transformations. They allow simple molecules to be clipped together to make complex new structures with potentially valuable properties.
A method that allows two click reactions to be done in tandem has recently been developed. But the libraries of new molecules that can be made using this double-click chemistry are so large that it is challenging to analyse them all.
Now, a team co-led by researchers from ShanghaiTech University in China has coupled the double-click reaction with rapid analysis based on affinity selection mass spectrometry and functional screening.
From a library of nearly 40,000 molecules, the team identified candidates that bind the glucagon-like-peptide-1 receptor, which is a target for treating obesity and type 2 diabetes.
References
- PNAS 120, e2220767120 (2023). doi: 10.1073/pnas.2220767120