Synthesis of Erythropoietins Site-Specifically Conjugated with Complex-Type N-Glycans.
The biological activity of the glycoprotein hormone erythropoietin (EPO) is dependent mainly on the structure of its N-linked glycans. We aimed to readily attach defined N-glycans to EPO through copper-catalyzed azide alkyne cycloaddition. EPO variants with an alkyne-bearing non-natural amino acid (Plk) at the N-glycosylation sites 24, 38, and 83 were obtained by amber suppression followed by protein purification and refolding. Click conjugation of the alkynyl EPOs with biantennary N-glycan azides provided biologically active site-specifically modified EPO glycoconjugates.
['Streichert|Katharina|K|', 'Seitz|Carina|C|', 'Hoffmann|Eugenia|E|', 'Boos|Irene|I|', 'Jelkmann|Wolfgang|W|', 'Brunner|Thomas|T|', 'Unverzagt|Carlo|C|', 'Rubini|Marina|M|0000-0002-3102-2558']
D004921:Erythropoietin D006801:Humans D008958:Models, Molecular D015394:Molecular Structure D011134:Polysaccharides
glycoproteins click chemistry protein engineering protein modification synthetic glycans