Machida Takuya, Lang Kathrin, Xue Lin, Chin Jason W, Winssinger Nicolas
†Department of Organic Chemistry, NCCR Chemical Biology, University of Geneva, 30 quai Ernest Ansermet, 1211 Geneva, Switzerland.
‡Technical University Munich, Institute for Advanced Study, Department of Chemistry, 4 Lichtenbergstraße, 85748 Garching, Germany.
Bioconjug Chem. 2015 May 20;26(5):802-6. doi: 10.1021/acs.bioconjchem.5b00101. Epub 2015 Apr 24.
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.
在糖生物学和治疗应用中，高效获取经聚糖位点特异性修饰的蛋白质非常重要。在此，我们报道了一种通过四嗪与反式环辛烯之间的逆需求狄尔斯-阿尔德反应实现的生物相容性蛋白质糖基共轭。通过糖基叠氮化物与炔基-四嗪加合物之间的铜催化炔基叠氮环加成反应（CuAAC）一步获得四嗪功能化的聚糖。在遗传编码了反式环辛烯衍生赖氨酸的靶蛋白上进行化学选择性位点特异性糖基共轭。糖基共轭在纯化的蛋白质上进行完全，并在大肠杆菌中显示对靶蛋白具有选择性。
