His-Tagging: Exploring Precise Chemical Modification of Histidine-Containing Bioactive Peptide Sequences

Abstract The modification of biomolecules, particularly peptides, has garnered considerable attention from researchers, effectively serving as a connection between chemistry and biology. The modification of peptides can facilitate, among others, the generation of peptide drugs, antibody–drug conjugates, and probes for molecular imaging. Herein, we have carefully curated reactions and chemical transformations of bioactive peptide sequences equipped with histidine amino acids that are conducive for biological applications. This Account also highlights strategies for the chemical modification of histidine that might capture the imagination of both peptide researchers and synthetic chemists. 1 Introduction 2 Histidine Modification in Bioactive Peptides and Proteins 3 Remote Bioactive Peptides and Protein Modification Adjacent to Histidine 4 Conclusions and Future Directions