Synthesis of neoglycopeptides and analyses of their biodistribution in vivo to identify tissue specific uptake and novel putative membrane lectins.
Complex type N-linked oligosaccharides derived from fetuin, fibrinogen and thyroglobulin were coupled to acetyltyrosine affording a series of neoglycopeptides with retention of terminal structures and the beta-anomeric configuration of their reducing end N-acetylglycosamine residue. The neoglycopeptides thus synthesized could be labelled to high specific activities with 125I in the aromatic side chain of tyrosine. Analysis of the fate of these neoglycopeptides in conjunction with inhibition with asialofetuin and oligosaccharides of defined structure in mice in vivo revealed the uptake of galactosylated biantennary compound by kidneys, in addition to the known itinerary of triantennary galactosylated complex oligosaccharide from fetuin to liver and the galactosylated biantennary chain with fucosylation in the core to bone marrows. On the other hand, the agalacto, aglucosamino biantennary chains with and without fucosylation in the core region are taken up by submaxillary glands while the conserved trimannosyl core with fucose is primarily concentrated in stomach tissue. These studies thus define new routes for the uptake of complex N-linked glycans and also subserve to identify lectins presumably involved in their recognition.
Gupta
D
D
Molecular Biophysics Unit, Indian Institute of Science, Bangalore.
Surolia
A
A
D000818:Animals; D002240:Carbohydrate Sequence; D006020:Glycopeptides / Q000138:chemical synthesis* / Q000378:metabolism / Q000493:pharmacokinetics; D006031:Glycosylation; D007457:Iodine Radioisotopes; D037102:Lectins / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000138:chemical synthesis; D014018:Tissue Distribution
D006020:Glycopeptides; D007457:Iodine Radioisotopes; D037102:Lectins; D008565:Membrane Proteins; D009844:Oligosaccharides