The emergence of sulfo-click amidation in kinetic target-guided synthesis

Sulfo-click is a chemoselective and biocompatible reaction between thioacids and sulfonyl azides that forms highly versatile N-acylsulfonamides, interesting bioisosteres of carboxylic acids. This reaction is useful for chemists and biologists and has many applications in medicinal chemistry, drug discovery, bioconjugation chemistry, and chemical biology. Sulfo-click amidations have been extensively used in kinetic target-guided synthesis (KTGS) to identify modulators of protein-protein interactions (PPIs). Different variants of KTGS screening, such as binary and multi-fragments, as well as one-pot deprotection/amidation strategies, have been successfully performed using sulfo-click chemistry. In this mini-review, we discuss the recent developments of sulfo-click amidation in KTGS and provide directions for future research.