Open AccessSite-Specific Glycoconjugation of Protein via Bioorthogonal Tetrazine Cycloaddition with a Genetically Encoded trans-Cyclooctene or Bicyclononyne
Author(s) -
Takuya Machida,
Kathrin Lang,
Lin Xue,
Jason W. Chin,
Nicolas Winssinger
Publication year - 2015
Publication title -
bioconjugate chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.279
H-Index - 172
eISSN - 1520-4812
pISSN - 1043-1802
DOI - 10.1021/acs.bioconjchem.5b00101
Subject(s) - tetrazine , bioorthogonal chemistry , chemistry , cyclooctene , cycloaddition , azide , glycan , bioconjugation , alkyne , combinatorial chemistry , glycobiology , biochemistry , click chemistry , glycoprotein , organic chemistry , catalysis
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.