Exploiting Protein N-Terminus for Site-Specific Bioconjugation

Although a plethora of chemistries have been developed to selectively decorate proteinmolecules, novel strategies continue to be reported with the final aim of improving selectivity andmildness of the reaction conditions, preserve protein integrity, and fulfill all the increasing requirements of the modern applications of protein conjugates. The targeting of the protein N-terminalalpha-amine group appears a convenient solution to the issue, emerging as a useful and uniquereactive site universally present in each protein molecule. Herein, we provide an updated overview ofthe methodologies developed until today to afford the selective modification of proteins through thetargeting of the N-terminal alpha-amine. Chemical and enzymatic strategies enabling the selectivelabeling of the protein N-terminal alpha-amine group are described.