Targeting of synthetically glycosylated human placental glucocerebrosidase.
Human placental beta-glucocerebrosidase modified by covalent attachment of N2-(N2, N6-bis [3-(alpha-D-mannopyranosylthio)propionyl]-L- lysyl)-N6-[3-(alpha-D-mannopyranosylthio)propionyl]-L-lysine was administered to rats by intravenous injection. Comparison of enzyme distribution in isolated liver cell populations indicates an increase in enzyme-specific activity of 18-fold in nonparenchymal cells and only 1.5-fold to hepatocytes compared to uninjected control animals. This macrophage-specific delivery of an active lysosomal enzyme has potential for application in enzyme replacement trials.
D000818:Animals; D005959:Glucosidases / Q000008:administration & dosage*; D005962:Glucosylceramidase / Q000008:administration & dosage* / Q000378:metabolism; D006020:Glycopeptides / Q000008:administration & dosage; D006801:Humans; D007275:Injections, Intravenous; D007728:Kupffer Cells / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D010920:Placenta / Q000201:enzymology*; D051381:Rats
D006020:Glycopeptides; C033688:trimannosyldilysine; D005959:Glucosidases; D005962:Glucosylceramidase