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Updated: May 11, 2026

Genetic Incorporation of Biosynthesized L-dihydroxyphenylalanine (DOPA) and Its Application to Protein Conjugation
Published on: August 24, 2018
Protein conjugation with genetically encoded unnatural amino acids
Chan Hyuk Kim1, Jun Y Axup, Peter G Schultz
1California Institute for Biomedical Research, 11119 N. Torrey Pines Road, La Jolla, CA 92037, United States.
Abstract:
The site-specific incorporation of unnatural amino acids with orthogonal chemical reactivity into proteins enables the synthesis of structurally defined protein conjugates. Amino acids containing ketone, azide, alkyne, alkene, and tetrazine side chains can be genetically encoded in response to nonsense and frameshift codons. These bio-orthogonal chemical handles allow precise control over the site and stoichiometry of conjugation, and have enabled medicinal chemistry-like optimization of the physical and biological properties of protein conjugates, especially the next-generation protein therapeutics.
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