Enhanced intracellular stability of dextran-horse radish peroxidase conjugate: an approach to enzyme replacement therapy.
Horse radish peroxidase (HRP), a mannose-containing glycoprotein was covalently modified by conjugation with dextran. The rapid uptake of HRP by the liver is markedly inhibited by mannan. The uptake of dextran-HRP conjugate by the liver, though lower compared to that of the free enzyme, is also partially inhibited by mannan. Liposomes were therefore used as carriers for delivering the free and the modified HRP to the liver. The dextran-HRP conjugate showed greater stability intracellularly as compared to the free enzyme. The enhanced stability of enzymes upon their extensive glycosylation with nondegradable sugar polymers would be of importance in extending the catalytic life of therapeutically active enzymes and thereby improve their therapeutic potential for the treatment of certain enzyme deficiency disorders.
Mumtaz
S
S
Department of Biochemistry, University of Delhi, India.
Bachhawat
B K
BK
D002850:Chromatography, Gel; D003911:Dextrans / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004337:Drug Carriers; D004591:Electrophoresis, Polyacrylamide Gel; D004795:Enzyme Stability; D006735:Horseradish Peroxidase / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008081:Liposomes / Q000008:administration & dosage; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008247:Lysosomes / Q000201:enzymology; D008351:Mannans / Q000494:pharmacology; D008930:Mitochondria, Liver / Q000201:enzymology
D003911:Dextrans; D004337:Drug Carriers; D008081:Liposomes; D008351:Mannans; C076786:dextran-horseradish peroxidase conjugate; D006735:Horseradish Peroxidase