Bioorganische Chemie, Gebäude NW1, Universität Bayreuth, 95440, Bayreuth, Germany.
Angew Chem Int Ed Engl. 2018 Oct 26;57(44):14543-14549. doi: 10.1002/anie.201807742. Epub 2018 Oct 11.
The occurrence of α1,6-linked core fucose on the N-glycans of mammalian glycoproteins is involved in tumor progression and reduces the bioactivity of antibodies in antibody-dependent cell-mediated cytotoxicity (ADCC). Since core-fucosylated N-glycans are difficult to isolate from natural sources, only chemical or enzymatic synthesis can provide the desired compounds for biological studies. A general drawback of chemical α-fucosylation is that the chemical assembly of α1,6-linked fucosides is not stereospecific. A robust and general method for the α-selective fucosylation of acceptors with primary hydroxy groups in α/β ratios exceeding 99:1 was developed. The high selectivities result from the interplay of an optimized protecting group pattern of the fucosyl donors in combination with the activation principle and the reaction conditions. Selective deprotection yielded versatile azides of all mammalian complex-type core-fucosylated N-glycans with 2-4 antennae and optional bisecting GlcNAc.
哺乳动物糖蛋白 N-糖链上 α1,6-连接岩藻糖的存在与肿瘤进展有关，并降低抗体依赖细胞介导的细胞毒性 (ADCC) 中抗体的生物活性。由于核心岩藻糖基化的 N-糖链很难从天然来源中分离出来，因此只有化学或酶合成才能为生物学研究提供所需的化合物。化学 α-岩藻糖基化的一个普遍缺点是 α1,6-连接的岩藻糖苷的化学组装不是立体特异性的。开发了一种用于在 α/β 比超过 99:1 的情况下对具有伯羟基的受体进行 α-选择性岩藻糖基化的稳健且通用的方法。高选择性源于优化的糖基供体保护基模式与活化原理和反应条件的相互作用。选择性脱保护得到了所有具有 2-4 个天线和可选的双分 GlcNAc 的哺乳动物复杂型核心岩藻糖基化 N-糖链的多功能叠氮化物。
