Polyethylene glycol-modified enzyme

Acid-catalyzed matrices, kinetics of controlled release, 170-179 Active targeting, definition, 276 Adenosine deaminase, activity of polyethylene glycol modified enzymes, 98-99 Adjuvax... 

Inada, Y., Takahashi, K., Yoshimoto, T., Ajima, A., Matsushima, A., and Saito, Y. (1986) Applications of polyethylene glycol-modified enzymes in biotechnological processes Organic solvent-soluble enzymes. Trends Biotechnol. 4, 190-194. 

Q. Yao, S. Yabuki and F. Mizutani, Preparation of a carbon paste/alcohol dehydrogenase electrode using polyethylene glycol-modified enzyme and oil-soluble mediator, Sens. Actuators B Chem., 65(1-3) (2000) 147-149. A. Morales, F. Cespedes, E. Martinez-Fabregas and S. Alegret, Ethanol amperometric biosensor based on an alcohol oxidase-graphite-polymer biocomposite, Electrochim. Acta, 43(23) (1998) 3575-3579. 

Polyethylene glycol modified enzymes w/cyclodextrin (Kyowa Medex)... 

Sugiuchi H, Uji Y, Okabe H, Me T, Uekama K, Kayahara N, Miyauchi K. Direct measurement of high-density lipoprotein cholesterol in serum with polyethylene glycol-modified enzymes and sulfated alpha-cyclodextrin. Clin Chem 1995 41 717-23. 

Yabuki S, Mizutani F, Katsura T (1994) Choline-sensing electrode based on polyethylene glycol-modified enzyme and mediator. Sensor Actuat B Chtan 20 159-162... 

Chapters are also included on yeast-mediated stereoselective biocatalysis, stereoselective synthesis of steroids, chemo-enzymatic synthesis of enantiopure arylpropionic acids, supercritical carbon dioxide as a solvent in enzyme catalysis, state-of-the-art techniques in enzyme immobilization, biocatalysis by polyethylene glycol-modified enzymes, and enzymatic deprotection techniques in organic synthesis. 

ADA deficiency is most commonly associated with these mutations of the ADA structural gene that result in either unstable or inactive enzyme protein. Immune reconstitution would be achieved by enzyme replacement therapy with polyethylene glycol-modified bovine ADA (PEG-AD A), alone or in combination with gene therapy (H3). 

Lipase has been used in organic solvents to produce useful compounds. For example, Zark and Klibanov (8) reported wide applications of enzymes to esterification in preparing optically active alcohols and acids. Inada et al (9) synthesized polyethylene glycol-modified lipase, which was soluble in organic solvent and active for ester formation. These data reveal that lipases are very useful enzymes for the catalysis different types of reactions with rather wide substrate specificities. In this study, it was found that moditied lipase could also synthesize esters and various lipids in organic solvents. Chemically moditied lipases can help to solve today s problems in esteritication and hopefully make broader use of enzymatic reactions that are attractive to the industry. 

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... 

Polyethylene glycol is used to make the enzymes soluble in organic solvents [88], and high reaction yields have been obtained with polyethylene-glycol-modified chymotrypsin [89], and papain in benzene [90], Enzymatic modification reactions with deacylation, via aminolysis, of an intermediate covalent acyl-enzyme also support the mechanism of transpeptidation in kinetically controlled peptide syn-... 

Janssen, A. E. M., Klabbers, C., Franssen, M. C. R. and Vantriet, K. (1991) Enzymatic-synthesis of carbohydrate esters in 2-p5urolidone. Enzyme Microb. Technol., 13, 565-572. Inada, Y., Nishimura, H., Takahashi, K. et al. (1984) Ester synthesis catalysed by polyethylene glycol-modified lipase in benzene. Biochem. Biophys. Res. Commim., 122, 845-850. 

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. 

Alternatively, the enzyme can be modified such that it dissolves in a hydrophobic ionic liquid with retention of activity. This approach was demonstrated with cyt c, which, when covalently modified with polyethylene glycol (PEG), dissolved in [EMIm][ Tf2N] with retention of activity. The best results were obtained when the molecular weight of the polymer chain was >2000 [88]. Similarly, a copolymer of PEG and maleic anhydride solubilized subtilisin in [EMIm][NTf2] and a range of similar ionic liquids with good retention of activity and operational stability [89, 90]. 

Polyethylene glycol) (PEG) molecules attached to adenosine deaminase (ADA) have been used in patients exhibiting symptoms of the severe combined immunodeficiency syndrome (SCID) caused by ADA deficiency. The modified enzyme has a plasma half-life of weeks as compared to the unmodified enzyme (minutes) (248). PEG-L-asparaginase has induced remissions in patients with non-Hodgkin s lymphoma (248). However, one disadvantage of PEG-enzyme treatment is its expense, ie, a year s treatment costs about 60,000 (248). 

The enzyme preparation used was uricase modified with polyethylene glycol, from Enzon, or plasma from patients is treated with PEC-uricase. 

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