Synthesis and molecular tumbling properties of sialyl Lewis X and derived neoglycolipids

Abstract

The sialyl Lewis X (sLeX) epitope has become a prominent target for biological studies because of its role in inflammation through binding to selectins. This epitope is located at the terminal end in glycosphingolipids and a lactose unit serves as spacer to the ceramide moiety. This paper focuses on the influence of the spacer structure and spacer length in regard to the mobility of the sLeX epitope. To this end sLex neoglycolipids 1a-c, with one, two, or three lactose units as spacer between the sLeX tetrasaccharide epitope and the membrane anchor, were synthesized. The synthetic strategy was also applied to the synthesis of the corresponding Lewis X (LeX) derivatives. The glycolipids were inserted in model membranes, and the tumbling frequencies of the sLex tetrasaccharide epitopes were then analysed by NMR spectroscopy. A nonaethylene glycol spacer decouples the carbohydrate moiety from the membrane mobility while (oligo-)lactoses act as more rigid distance keepers between the Lewis epitope and the surface of the membrane. Quantification of the different degrees of decoupling was possible by analysis of rotational correlation times.