蛋白质的糖基化是一类重要的翻译后修饰，极大地增加了蛋白质结构的复杂性和功能的多样性。其时空特异、双向可逆的动态属性，给构效关系研究带来巨大挑战。α-肌营养不良蛋白聚糖（α-DG）是细胞表面重要的粘附受体，通过core M3型O-甘露糖基化实现与配体相互作用的动态调控，其糖基化水平的异常往往影响着多种疾病的发生发展（统称为“肌营养不良综合征”），而且与肿瘤侵袭迁移和病毒入侵等病理过程密切相关。由于core M3型甘露糖链结构高度复杂，完整糖链结构的解析近期刚刚完成，其与疾病相关的分子机制尚不明确。本项目拟发展高效的化学合成策略，模拟core M3型糖链结构的内源合成过程，设计并合成基于core M3型特异性糖链结构的一系列分子探针，进行糖链依赖性的α-DG胞外结构域糖肽与天然配体层粘连蛋白的相互作用研究，在分子层面揭示糖链结构和配体亲和力的构效关系，为阐明相关疾病的发病机制奠定基础。

Protein glycosylation is an important type of post-translational modification, which adds the complexity of protein structure and contributes to the versatility of protein function. The time-dependent, site-specific and highly reversible nature of such modification process poses tremendous challenge to the study of the underlying structure-function relationship. α-Dystroglycan is a cell surface receptor which undergoes extensive glycosylation, where core M3 type of O-mannosylation mediates a variety of physiological processes via interaction with extracellular proteins (laminin, agrin, percelan, etc). Aberrant O-mannosylation accounts for various disease-related malfunctions, including various types of dystroglycanopathies, cancer progression and viral entry. Owing to the complex structure of core M3 type of mannosyl glycan, which was not fully elucidated until recently, the disease relevance remains elusive. To address this issue, this research project aims to mimic the biosynthetic pathway of such glycans by chemical synthesis, to afford the biotin-labelled α-DG ectodomain glycopeptide bearing mannosyl glycans of respective length, and to probe the ligand binding process. The current study paves way for better understanding of the glycan chain specific disease relevance on molecular level.