O-GalNAc 聚糖，也称为粘蛋白型 O-聚糖，是身体各个粘膜部位粘蛋白的主要成分，也普遍表达在细胞表面和分泌蛋白上。它们在广泛的生理和病理过程中发挥着至关重要的作用，包括肿瘤的生长和进展。此外，在不同的疾病状态下经常观察到 O-GalNAc 聚糖表达的改变。致力于揭示 O-GalNAc 聚糖的结构与功能关系的研究导致了疾病生物标志物和诊断工具的发现以及基于 O-糖肽的癌症疫苗的开发。其中许多工作需要氨基酸连接的 O-GalNAc 核心结构作为构建模块来组装复杂的 O-聚糖和糖肽。有八个核心结构（核心一到八），所有粘蛋白型 O-聚糖均源自其。在本协议中，我们描述了在实际规模中从多功能前体中所有八个核心的首次发散合成。该协议包括（i）从市售材料化学合成正交保护的前体（3天），（ii）五个独特的糖基供体的化学合成（每个供体1-2天）和（iii）前体的选择性脱保护以及八个核心的组装（每个核心需要 2-4 天）。该方法可用于制备与丝氨酸、苏氨酸和酪氨酸连接的O-GalNAc核心，然后可直接用于固相糖肽合成或复杂O-聚糖的化学酶法合成。该程序使具有基本有机化学技能的研究人员能够同时制备任何所需的 O-GalNAc 核心或所有八个核心的克级。© 2024。Springer Nature Limited。

O-GalNAc glycans, also known as mucin-type O-glycans, are primary constituents of mucins on various mucosal sites of the body and also ubiquitously expressed on cell surface and secreted proteins. They have crucial roles in a wide range of physiological and pathological processes, including tumor growth and progression. In addition, altered expression of O-GalNAc glycans is frequently observed during different disease states. Research dedicated to unraveling the structure-function relationships of O-GalNAc glycans has led to the discovery of disease biomarkers and diagnostic tools and the development of O-glycopeptide-based cancer vaccines. Many of these efforts require amino acid-linked O-GalNAc core structures as building blocks to assemble complex O-glycans and glycopeptides. There are eight core structures (cores one to eight), from which all mucin-type O-glycans are derived. In this protocol, we describe the first divergent synthesis of all eight cores from a versatile precursor in practical scales. The protocol involves (i) chemical synthesis of the orthogonally protected precursor (3 days) from commercially available materials, (ii) chemical synthesis of five unique glycosyl donors (1-2 days for each donor) and (iii) selective deprotection of the precursor and assembly of the eight cores (2-4 days for each core). The procedure can be adopted to prepare O-GalNAc cores linked to serine, threonine and tyrosine, which can then be utilized directly for solid-phase glycopeptide synthesis or chemoenzymatic synthesis of complex O-glycans. The procedure empowers researchers with fundamental organic chemistry skills to prepare gram scales of any desired O-GalNAc core(s) or all eight cores concurrently.© 2024. Springer Nature Limited.