Yoshida Keisuke, Yang Bo, Yang Weizhun, Zhang Zeren, Zhang Jicheng, Huang Xuefei
Department of Chemistry, Michigan State University, 578 S. Shaw Lane, East Lansing, MI 48824 (USA).
Angew Chem Int Ed Engl. 2014 Aug 18;53(34):9051-8. doi: 10.1002/anie.201404625. Epub 2014 Jun 30.
Despite the ubiquitous presence of proteoglycans in mammalian systems, methodologies to synthesize this class of glycopeptides with homogeneous glycans are not well developed. Herein, we report the first synthesis of a glycosaminoglycan family glycopeptide containing two different heparan sulfate chains, namely the extracellular domain of syndecan-3. With the large size and tremendous structural complexity of these molecules, multiple unexpected obstacles were encountered during the synthesis, including high sensitivity to base treatment and the instability of glycopeptides with two glycan chains towards catalytic hydrogenation conditions. A successful strategy was established by constructing the partially deprotected single glycan chain containing glycopeptides first, followed by union of the glycan-bearing fragments and cleavage of the ester-type protecting groups. This work lays the foundation for preparing other members of this important class of molecules.
尽管蛋白聚糖在哺乳动物系统中普遍存在，但用于合成这类具有均匀聚糖的糖肽的方法尚未得到充分发展。在此，我们报告了首次合成一种含有两条不同硫酸乙酰肝素链的糖胺聚糖家族糖肽，即syndecan-3的细胞外结构域。由于这些分子的尺寸大且结构极其复杂，在合成过程中遇到了多个意想不到的障碍，包括对碱处理高度敏感以及具有两条聚糖链的糖肽在催化氢化条件下的不稳定性。通过首先构建含有部分脱保护的单聚糖链的糖肽，然后将含聚糖的片段连接并裂解酯型保护基团，建立了一种成功的策略。这项工作为制备这一重要分子类别的其他成员奠定了基础。
