Conformation of the polar headgroup of sphingomyelin and its analogues

The conformation of the polar headgroup of synthetic D-erythro-stearoylsphingomyelin (1), its L-threo-isomer (2) and phosphorothioyl analogues of 1 (3 and 4) has been studied in detail by high-resolution NMR spectroscopy. In both monomeric and aggregated states the phosphocholine function of 1 adopts the synclinal conformation (alpha 5 torsional angle), in analogy with phosphatidylcholine (Hauser, H., Guyer, W., Pascher, I., Skrabal, P. and Sundell, S. (1980) Biochemistry 19, 366-373). The conformation about the C1-C2 bond (theta 1 angle) of the sphingosine backbone is predominantly -synclinal, analogously to the conformation of the crystalline galactosyl cerebroside (Pascher, I. and Sundell, S. (1977) Chem. Phys. Lipids 20, 175-191). In contrast, the L-threo-isomer displays unrestricted rotation about C1-C2 bond. The possibility of the existence of a hydrogen bond between the 3-hydroxyl function and the bridged oxygen atom of sphingosine responsible for the different conformation of 1 and 2 is discussed. The modification of the phosphate function in 1 with sulfur has no significant effect on the conformation of the resulting analogues. The conformation of all studied compounds about the C-O phosphoester bonds (alpha 1 and alpha 4 torsion angles) is mainly antiperiplanar. Similar to other double-chain phospholipids, sphingomyelin shows a preference towards the antiperiplanar conformation about the C2-C3 bond.