Mohamed Basant, Rohokale Rajendra, Yan Xin, Ghanim Amany M, Osman Nermine A, Abdel-Fattah Hanan A, Guo Zhongwu
Department of Chemistry, University of Florida, Gainesville, FL 32611, USA.
Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt.
Molecules. 2025 Jun 20;30(13):2667. doi: 10.3390/molecules30132667.
β-Lactosylceramide (β-LacCer) is not only a key intermediate in the biosynthesis of complex glycosphingolipids (GSLs) but also an important regulator of many biological processes. To facilitate the investigation of β-LacCer and other GSLs, a series of β-LacCer analogs with an azido group at the 6--position of the D-galactose in lactose and varied forms of the ceramide moiety were synthesized from commercially available lactose in sixteen linear steps by a versatile and diversity-oriented strategy, which engaged lipid remodeling and glycan functionalization at the final stage. These azide-labeled β-LacCer analogs are flexible and universal platforms that are suitable for further functionalization with other molecular tags via straightforward and biocompatible click chemistry, thereby paving the way for their application to various biological studies.
β-乳糖神经酰胺（β-LacCer）不仅是复杂糖鞘脂（GSLs）生物合成中的关键中间体，也是许多生物过程的重要调节剂。为了便于对β-LacCer和其他GSLs进行研究，通过一种通用的、面向多样性的策略，从市售乳糖出发，经16个线性步骤合成了一系列在乳糖的D-半乳糖6位带有叠氮基且神经酰胺部分形式各异的β-LacCer类似物，该策略在最后阶段涉及脂质重塑和聚糖功能化。这些叠氮标记的β-LacCer类似物是灵活通用的平台，适用于通过直接且生物相容的点击化学与其他分子标签进行进一步功能化，从而为它们应用于各种生物学研究铺平了道路。
