Affinity selection of double-click triazole libraries for rapid discovery of allosteric modulators for GLP-1 receptor.
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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.
- PNAS 120, e2220767120 (2023). doi: 10.1073/pnas.2220767120