Bello Claudia, Wang Shuo, Meng Lu, Moremen Kelley W, Becker Christian F W
Fakultät Chemie, Institut für Biologische Chemie, Universität Wien, Währinger Strasse 38, 1090 Vienna (Austria).
Complex Carbohydrate Research Center, University of Georgia, Athens (USA).
Angew Chem Int Ed Engl. 2015 Jun 22;54(26):7711-5. doi: 10.1002/anie.201501517. Epub 2015 May 15.
Research aimed at understanding the specific role of glycosylation patterns in protein function would greatly benefit from additional approaches allowing direct access to homogeneous glycoproteins. Herein the development and application of an efficient approach for the synthesis of complex homogenously glycosylated peptides based on a multifunctional photocleavable auxiliary is described. The presence of a PEG polymer within the auxiliary enables sequential enzymatic glycosylation and straightforward isolation in excellent yields. The auxiliary-modified peptides can be directly used in native chemical ligations with peptide thioesters easily obtained by direct hydrazinolysis of the respective glycosylated peptidyl resins and subsequent oxidation. The ligated glycopeptides can be smoothly deprotected by UV irradiation. We apply this approach to the preparation of variants of the epithelial tumor marker MUC1 carrying one or more Tn, T, or sialyl-T antigens.
旨在了解糖基化模式在蛋白质功能中具体作用的研究，将极大地受益于其他能够直接获取均一糖蛋白的方法。本文描述了一种基于多功能光可裂解辅助剂合成复杂均一糖基化肽的高效方法的开发与应用。辅助剂中聚乙二醇聚合物的存在使得能够进行顺序酶促糖基化，并以优异的产率直接分离。辅助剂修饰的肽可直接用于与肽硫酯的天然化学连接，肽硫酯可通过对相应糖基化肽树脂直接进行肼解并随后氧化轻松获得。连接后的糖肽可通过紫外线照射顺利脱保护。我们将此方法应用于制备携带一个或多个Tn、T或唾液酸化-T抗原的上皮肿瘤标志物MUC1的变体。
