Ganglioside GD1 alpha analogues as high-affinity ligands for myelin-associated glycoprotein (MAG)

The first systematic synthesis of ganglioside GD1 alpha analogues carrying N-acetyldeoxyneuraminic acids linked to C-6 of the GalNAc residue was accom plished. The suitably protected GM1b pentasaccharide derivative was regiose lectively glycosylated with the phenyl 2-thioglycosides of 7-deoxy, 8-deoxy , and 9-deoxy-N-acetylneuraminic acid promoted by N-iodosuccinimide (NIS)-t rifluoromethanesulfonic acid (TfOH) in acetonitrile, and the resulting hexa saccharides were converted to the target GD1 alpha analogues. All of the an alogues retained excellent efficiency in supporting the adhesion to myelin- associated glycoprotein (MAG), raising the possibility that the internal si alic acid linked to the GalNAc residue may be replaced by other anionic sub stituents, in contrast to the terminal sialic acid, which is essential for MAG binding. (C) 1999 Elsevier Science Ltd. All rights reserved.