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Updated: Apr 14, 2026

Genetic Encoding of a Non-Canonical Amino Acid for the Generation of Antibody-Drug Conjugates Through a Fast Bioorthogonal Reaction
Published on: September 14, 2018
Site-Specific Glycoconjugation of Protein via Bioorthogonal Tetrazine Cycloaddition with a Genetically Encoded
Takuya Machida1, Kathrin Lang2, Lin Xue3
1†Department of Organic Chemistry, NCCR Chemical Biology, University of Geneva, 30 quai Ernest Ansermet, 1211 Geneva, Switzerland.
Abstract:
Efficient access to proteins modified site-specifically with glycans is important in glycobiology and for therapeutic applications. Herein, we report a biocompatible protein glycoconjugation by inverse demand Diels-Alder reaction between tetrazine and trans-cyclooctene. Tetrazine functionalized glycans were obtained in one step by CuAAC (Cu-catalyzed alkyne azide cycloaddition) between glycosyl azide and an alkyne-tetrazine adduct. Site-specific glycoconjugation was performed chemoselectively on a target protein in which a trans-cyclooctene derivatized lysine was genetically encoded. Glycoconjugation proceeded to completion on purified protein and was shown to be selective for the target protein in E. coli.
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