Key Laboratory of Chemical Biology of Natural Products (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China.
National Glycoengineering Research Center, Shandong University, Jinan 250012, China.
Sci Adv. 2023 Feb 17;9(7):eade4770. doi: 10.1126/sciadv.ade4770.
The introduction of unnatural chemical moieties into glycosaminoglycans (GAGs) has enormous potential to facilitate studies of the mechanism and application of these critical, widespread molecules. Unnatural -acetylhexosamine analogs were metabolically incorporated into the capsule polysaccharides of and via bacterial metabolism. Targeted metabolic labeled hyaluronan and the precursors of heparin and chondroitin sulfate were obtained. The azido-labeled polysaccharides (purified or in capsules) were reacted with dyes, via bioorthogonal chemistry, to enable detection and imaging. Site-specific introduction of fluorophores directly onto cell surfaces affords another choice for observing and quantifying bacteria in vivo and in vitro. Furthermore, azido-polysaccharides retain similar biological properties to their natural analogs, and reliable and predictable introduction of functionalities, such as fluorophores, onto azido--hexosamines in the disaccharide repeat units provides chemical tools for imaging and metabolic analysis of GAGs in vivo and in vitro.
将非天然化学基团引入糖胺聚糖（GAGs）中，具有极大的潜力来促进对这些关键的、广泛存在的分子的机制和应用的研究。非天然乙酰己糖类似物通过细菌代谢被代谢纳入 和 的荚膜多糖中。目标代谢标记的透明质酸以及肝素和硫酸软骨素的前体被获得。叠氮标记的多糖（纯化或在胶囊中）通过生物正交化学与染料反应，以实现检测和成像。荧光团的定点引入为观察和定量体内和体外细菌提供了另一种选择。此外，叠氮多糖保留与其天然类似物相似的生物学特性，并且可靠且可预测地将功能（例如荧光团）引入到二糖重复单元中的叠氮-己糖胺中，为 GAGs 的体内和体外成像和代谢分析提供了化学工具。
