Late-Stage Peptide Modification with Salicylaldehyde Tag Enhances Affinity for Nuclear Factor kappa B Essential Modulator

The late-stage peptide functionalization with salicylaldehyde (SA) tags is described here as a versatile design of potential Lys-engaging, reversible-covalent ligands. This approach was applied to a known binder for NEMO, a protein involved in the activation of the pro-inflammatory transcription factor NFκB. Fluorescence anisotropy screening led to the identification of SA-tagged peptides with higher affinity than the wild-type sequence.