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. 2025 Jun 20;30(13):2667.
doi: 10.3390/molecules30132667.

Synthesis of Azide-Labeled β-Lactosylceramide Analogs Containing Different Lipid Chains as Useful Glycosphingolipid Probes

Basant Mohamed  1   2 , Rajendra Rohokale  1 , Xin Yan  1 , Amany M Ghanim  2 , Nermine A Osman  2 , Hanan A Abdel-Fattah  2 , Zhongwu Guo  1   3
Affiliations

Synthesis of Azide-Labeled β-Lactosylceramide Analogs Containing Different Lipid Chains as Useful Glycosphingolipid Probes

Basant Mohamed et al. Molecules. .

Abstract

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-C-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.

Keywords: azide; carbohydrates; glycolipids; glycosphingolipids; lactose; lipids; synthesis; β-Lactosylceramide.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(A) The biosynthetic pathways for globo-, isoglobo-, ganglio-, lacto-, and neolecto-series GSLs, utilizing β-LacCer as the key intermediate, and some key enzymes involved, and structures of (B) a representative β-LacCer with the most common (18:1/18:0) lipid form found in mammals and (C) designed β-LacCer analogs with different lipid forms as useful probes to study β-LacCer and other GSLs.
Scheme 1
Scheme 1
Preparation of 10—the key and common building block for the synthesis of all designed probes in the present work.
Scheme 2
Scheme 2
Assembly of the designed β-LacCer probes 1a–d.
See this image and copyright information in PMC

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