Effect of protein chemical hydrophobization on antiglucose oxidase immunoglobulin production in mouse.
One problem resulting from the therapeutic use of enzymes is the adverse immunological reactions. In order to study the immunoglobulin production elicited into mice by different derivatives of an enzyme, glucose oxidase was chosen as a model. The immunoglobulin productions induced by apoglucose oxidase, prepared by removing flavine adenine dinucleotide from the native enzyme through an acidic treatment and devoid of enzymatic activity, by metaperiodate-oxidized glucose oxidase that lost about 50% of its carbohydrate moiety, and by propyl aliphatic chains-coupled glucose oxidase were as intense as that induced by native glucose oxidase. On the other hand, coupling hexyl aliphatic chains to the enzyme did change its ability to stimulate antibody production. This hydrophobized preparation induced a low titer of antibody after repeated intravenous or subcutaneous injections. This result suggests a simple strategy for reducing the immunogenicity of foreign proteins and for decreasing the risk of immunological complications in enzyme therapy.
Shi
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Laboratory of Enzymatic Technology (U.R.A. no. 1442 of C.N.R.S.), University of Technology, Compiègne, France.
Domurado
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Domurado
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D000818:Animals; D001051:Apoenzymes / Q000276:immunology*; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005182:Flavin-Adenine Dinucleotide; D005949:Glucose Oxidase / Q000737:chemistry* / Q000276:immunology*; D007136:Immunoglobulins / Q000096:biosynthesis*; D051379:Mice; D010084:Oxidation-Reduction; D010504:Periodic Acid / Q000494:pharmacology; D011489:Protein Denaturation / Q000187:drug effects; D013329:Structure-Activity Relationship
D001051:Apoenzymes; D007136:Immunoglobulins; D010504:Periodic Acid; D005182:Flavin-Adenine Dinucleotide; C009288:metaperiodate; D005949:Glucose Oxidase