alpha1,4-Glucosidase-albumin polymers: in vitro properties and advantages for enzyme replacement therapy.
Soluble polymers of rat (or human) albumin and alpha-1,4-glucosidase are prepared using the cross-linking agent glutaraldehyde. The resulting polymer has an average molecular weight of 800 000 indicating an average composition of 12 albumin molecules for each enzyme molecule. Compared with an equivalent amount of free enzyme, the enzyme-albumin polymer has an increased resistance to heat denaturation (half-life of 15 h compared with 1 h for free enzyme at 37 degrees C) and to proteolysis by trypsin (half-life of 180 min compared with 10 min). The high degree of resistance to bioinactivation of the enzyme-albumin polymer is discussed in relation to requirements for enzyme replacement therapy in a range of metabolic diseases including type II glycogenosis (Pompe's disease) where alpha-1,4-glucosidase is the defective enzyme.
D000818:Animals; D001711:Biotransformation; D004800:Enzymes, Immobilized / Q000378:metabolism / Q000627:therapeutic use; D005959:Glucosidases / Q000627:therapeutic use*; D006008:Glycogen Storage Disease / Q000188:drug therapy*; D006009:Glycogen Storage Disease Type II / Q000188:drug therapy*; D006207:Half-Life; D006358:Hot Temperature; D006801:Humans; D008970:Molecular Weight; D051381:Rats; D012709:Serum Albumin / Q000378:metabolism / Q000627:therapeutic use*; D014357:Trypsin / Q000494:pharmacology; D000520:alpha-Glucosidases / Q000378:metabolism / Q000627:therapeutic use*
D004800:Enzymes, Immobilized; D012709:Serum Albumin; D005959:Glucosidases; C024982:alpha-1,4-glucosidase-albumin polymer; D000520:alpha-Glucosidases; D014357:Trypsin