Salicylaldehyde-bearing ligands can bind the protein targets forming imines with lysine-amino groups. This drug design improves the affinity and selectivity for specific biological targets. Given the abundance of lysine residues in proteins and the reversible covalent (RC) nature of ligand-protein interaction, SA-bearing ligands hold significant promise for future pharmaceutical applications.

Abstract

The installation of aldehydes into synthetic protein ligands is an efficient strategy to engage protein lysine residues in remarkably stable imine bonds and augment the compound affinity and selectivity for their biological targets. The high frequency of lysine residues in proteins and the reversibility of the covalent ligand-protein bond support the application of aldehyde-bearing ligands, holding promises for their future use as drugs. This review highlights the increasing exploitation of salicylaldehyde modules in various classes of protein binders, aimed at the reversible-covalent engagement of lysine residues.