Synthetic Strategies for Modified Glycosphingolipids and Their Design as Probes

The plasma membrane of cells contains a diverse array of lipids that provide important structural and biological features. Glycolipids are typically a minor component of the cell membrane and consist primarily of glycosphingolipids (GSLs). GSLs in vertebrates contain a multifarious assortment of glycan headgroups, which can be important to biological functions based on lipid-lipid and lipid-protein interactions. The design of probes to study these complex targets requires advanced synthetic methodologies. In this Review, we will discuss recent advances in chemical and chemoenzymatic synthesis of GSLs in conjunction with the use of these approaches to design new probes. Examples using either chemical or enzymatic semisynthesis methods starting from isolated GSLs will also be reviewed. Focusing primarily on vertebrate glycolipids, we will highlight examples of radionuclide, fluorophore, photoresponsive, and bioorthogonal tagged GSL probes.