Design and efficient synthesis of novel GM2 analogues with respect to the elucidation of the function of GM2 activator.
To elucidate the mechanism underlying the hydrolysis of the GalNAcbeta1-->4Gal linkage in ganglioside GM2 [GalNAcbeta1-->4(NeuAcalpha2-->3)Galbeta1-->4Glcbeta1-->1' Cer] by beta-hexosaminidase A (Hex A) with GM2 activator protein, we designed and synthesized two kinds of GM2 linkage analogues-6'-NeuAc-GM2 and alpha-GalNAc-GM2. In this paper, the efficient and systematic synthesis of these GM2 analogues was described. The highlight of our synthesis process is that the key intermediates, newly developed sialyllactose derivatives, were efficiently prepared in sufficient quantities; these derivatives directly served as highly reactive glycosyl acceptors and coupled with GalNTroc donors to furnish the assembly of GM2 tetrasaccharides in large quantities.
Komori
Tatsuya
T
Department of Applied Bioorganic Chemistry, Faculty of Applied Biological Sciences, Gifu University, Gifu, Japan.
Ando
Takayuki
T
Imamura
Akihiro
A
Li
Yu-Teh
YT
Ishida
Hideharu
H
Kiso
Makoto
M
D002236:Carbohydrate Conformation; D002518:Ceramides / Q000737:chemistry; D005678:G(M2) Ganglioside / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D006031:Glycosylation; D009844:Oligosaccharides / Q000737:chemistry
D002518:Ceramides; D009844:Oligosaccharides; D005678:G(M2) Ganglioside