RGD Cyclopeptide Equipped with a Lysine‐Engaging Salicylaldehyde Showing Enhanced Integrin Affinity and Cell Detachment Potency

Salicylaldehyde (SA) derivatives are emerging as useful fragments to obtain reversible‐covalent inhibitors interacting with the lysine residues of the target protein. Here the SA installation at the C terminus of an integrin‐binding cyclopeptide, leading to enhanced ligand affinity for the receptor as well as stronger biological activity in cultured glioblastoma cells is reported. A RGD cyclopeptide with a C‐terminal salicylaldehyde tag shows a higher affinity for integrin αVβ3 than control compounds. Covalent docking studies ascribe this increased affinity to a plausible formation of an intermolecular imine bond between salicylaldehyde and a Lys residue on the β3 integrin subunit.