O-GalNAc glycans on glycoproteins with eight different core structures sharing a common α-glycosidic linkage (O-GalNAc-α-Ser/Thr) are critical in various physiological and pathological processes. Among the eight O-GalNAc glycan cores, core 2 characterized by a GlcNAcβ1–6(Galβ1–3)GalNAc structural motif plays a significant role in regulating diverse biological processes, such as immune response modulation, adhesive properties of selectins, and gastrointestinal tract protection. However, the large-quantity synthesis of core 2 containing glyco-amino acids for downstream solid-phase peptide synthesis is challenging. In this work, we successfully employed a silver oxide for coupling a 2-azido-galactosyl chloride donor with two acceptors, Fmoc-Ser/Thr-O^tBu, respectively, for the large-scale synthesis of the two important intermediates, α-GalN₃–Fmoc-Ser/Thr-O^tBu, which can be further utilized for the large-scale synthesis of core 2 containing glyco-amino acids. The two intermediates, α-GalN₃–Fmoc-Ser/Thr-O^tBu, were utilized for synthesizing core 2 containing Fmoc-Ser/Thr-COOH. The synthesis of core 2 containing Fmoc-Ser-COOH was achieved on a 1.95 g scale, while the synthesis of core 2 containing Fmoc-Thr-COOH was achieved on a 0.38 g scale. Additionally, the synthesis of the 2-azido-galactosyl chloride donor was optimized into a three-step process with only one column chromatography purification. Finally, core 2 containing Fmoc-Ser/Thr-COOH were applied for the synthesis of glycosylated CCR1 and CCR5 N-terminal peptides.

中文翻译：

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氧化银促进含 α O-GalNAc 的糖氨基酸合成：合成含糖氨基酸的 Core 2 用于糖肽的固相合成


糖蛋白上的 O-GalNAc 聚糖具有 8 个不同的核心结构，共享一个共同的 α-糖苷键 （O-GalNAc-α-Ser/Thr），在各种生理和病理过程中至关重要。在 8 个 O-GalNAc 聚糖核心中，以 GlcNAcβ1-6（Galβ1-3）GalNAc 结构基序为特征的核心 2 在调节免疫反应调节、选择素的粘附特性和胃肠道保护等多种生物过程中发挥着重要作用。然而，用于下游固相肽合成的含有糖氨基酸的核心 2 的大量合成具有挑战性。在这项工作中，我们成功地采用了一种氧化银将 2-叠氮基-半乳糖酰给体与两个受体 Fmoc-Ser/Thr-O^tBu 偶联，用于两种重要中间体 α-GalN 3-Fmoc-Ser/Thr-O^tBu 的大规模合成，可进一步用于含糖氨基酸的核心 2 的大规模合成。两种中间体 α-GalN 3-Fmoc-Ser/Thr-O^tBu 用于合成含有 Fmoc-Ser/Thr-COOH 的核心 2。含有 Fmoc-Ser-COOH 的核心 2 的合成是在 1.95 g 的规模上实现的，而含有 Fmoc-Thr-COOH 的核心 2 的合成是在 0.38 g 的规模上实现的。此外，2-叠氮基半乳糖酰氯供体的合成被优化为三步法，仅需一次柱层析纯化。最后，将含有 Fmoc-Ser/Thr-COOH 的核心 2 用于合成糖基化 CCR1 和 CCR5 N 端肽。