Enzyme , polyethylene glycol conjugates

Experimental in vitro investigations utilizing liposomal-encapsulated and polyethylene glycol-conjugated SOD and catalase have demonstrated the potential value of such means in countering oxidative asbestos-related diseases (Freeman etal., 1985 Mossman etal., 1986). In addition to using supplementary endogenous antioxidant enzymes, the use of iron chelators like desferrioxamine... 

Brewerton LJ, Fung E, Snyder FF. Polyethylene glycol-conjugated adenosine phosphor-ylase development of alternative enzyme therapy for adenosine deaminase deficiency. Biochim Biophys Acta 2003 1637 171 177. 

The improvement of its activity and stability has been approach by the use of GE tools (see Refs. [398] and [399], respectively). A process drawback is the fact that the oxidation of hydrophobic compounds in an organic solvent becomes limited by substrate partition between the active site of the enzyme and the bulk solvent [398], To provide the biocatalyst soluble with a hydrophobic active site access, keeping its solubility in organic solvents, a double chemical modification on horse heart cytochrome c has been performed [400,401], First, to increase the active-site hydrophobicity, a methyl esterification on the heme propionates was performed. Then, polyethylene glycol (PEG) was used for a surface modification of the protein, yielding a protein-polymer conjugates that are soluble in organic solvents. 

Abuchowski, A., Kazo, G.M., Verhoest Jr., C.R., van Es, T., Kafkewitz, D., Nucci, M.L., Viau, A.T., and Davis, F.F. (1984) Cancer therapy with chemically modified enzymes. Anti-tumor properties of polyethylene glycol asparaginase conjugates. Cancer Biochem. Biophys. 7, 175-186. 

Chemical modification, particularly succinylation, or coupling to polyglycols, can also increase the plasma half-life of enzymes. Conjugation with polyethylene glycol [PEG H(OCH2CH2)nOH] has successfully been employed to stabilize and protect several therapeutic enzymes. Such modification, for example, increases the plasma half-life of superoxide dismutase from 5 h to over 30 h. PEG-coupled asparaginase was approved for general medical use by the FDA in 1994. 

Beckman, J. S., Minor, R. M., Jr., White, C. J., Repine, J., Rosen, G. M., and Freeman, B. A. (1988). Superoxide dismutase and catalase conjugated to polyethylene glycol increases endothelial enzyme activity and oxidant resistance. J. Biol. Chem. 263, 6584-6802. 

Another mode of enzyme replacement therapy is periodic administration of a polyethylene glycol-modified form of bovine intestinal ADA by intramuscular injection. The modified enzyme, which is prepared by conjugating polyethylene glycol with purified ADA (PEG-ADA), possesses a longer half-life as well as reduced immuno-genicity. As a consequence of this treatment, the correction... 

About 150 lipid molecules were present per 1 of enzyme. It was used to esterify 1-phenylethanol with lauric acid in isooctane, giving 95% conversion in 2 h. A lipid-coated lipase has also been used to esterify lauric acid with glycerol in sc carbon dioxide with 90% conversion.98 Catalase with less than 5% of its surface amino groups modified by the nonionic surfactant 9.7 had a higher activity in 1,1,1-trichloroethane than when the enzyme was conjugated with polyethylene glycol.99... 

---