Azido glycoside primer: a versatile building block for the biocombinatorial synthesis of glycosphingolipid analogues.
A lactoside primer, 12-azidododecyl beta-lactoside, was synthesized via the Koenigs-Knorr method by glycosylation of 1,12-dodecyldiol with perbenzoylated lactosyl bromide. The presence of the 2-O-acyl substituent in the donor gave the beta-lactoside, and an excess of acceptor ensured monoglycosylation of the diol. Mesylation of the omega-hydroxyl group in the aglycon, followed by displacement of the mesylate with azide and subsequent O-debenzoylation gave the desired omega-azidododecyl beta-lactoside. The azido glycoside primer was examined in mouse B16 melanoma cells for its feasibility as a building block for oligosaccharide biosynthesis. Uptake of the azido glycoside primer by B16 cells resulted in the sialylation of the galactose residue of the primer to give a glycosylated product having the same glycan as in ganglioside GM3. After 24 h incubation of B16 cells with the primers, the amount of sialylated omega-azidododecyl beta-lactoside primer was 75% of the amount of sialylated n-dodecyl beta-lactoside. However, after 48 h incubation, both primers gave equal amounts of the sialylated products. Interestingly, the remaining azido glycoside primer after 48 h incubation was 5.6-fold greater than that of the alkyl primer, indicating degradation of the alkyl primer to a larger extent than the omega-azido glycoside primer. The facile chemical synthesis and the efficient uptake in cells make the azido glycoside primer a versatile building block for the biocombinatorial synthesis of glycolipid oligosaccharides.
Kasuya
M C
MC
Department of Biomolecular Engineering, Tokyo Institute of Technology, Yokohama, Japan.
Wang
L X
LX
Lee
Y C
YC
Mitsuki
M
M
Nakajima
H
H
Miura
Y
Y
Sato
T
T
Hatanaka
K
K
Yamagata
S
S
Yamagata
T
T
D000818:Animals; D001386:Azides / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D001692:Biological Transport; D002455:Cell Division / Q000187:drug effects; D005679:G(M3) Ganglioside / Q000031:analogs & derivatives / Q000737:chemistry; D006027:Glycosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D006028:Glycosphingolipids / Q000096:biosynthesis* / Q000737:chemistry*; D006031:Glycosylation; D006801:Humans; D007785:Lactose / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D008546:Melanoma, Experimental; D051379:Mice; D015394:Molecular Structure; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014407:Tumor Cells, Cultured
C421632:12-azidododecyl lactoside; D001386:Azides; D005679:G(M3) Ganglioside; D006027:Glycosides; D006028:Glycosphingolipids; C008245:lactosides; D007785:Lactose