AB ZYMES (Antibody + Enzymes)  Monoclonal antibody  Catalytic activity  Artificial construct  Normal humans  Auto immune diseases PRINCIPLE  Lowering activation energy  Stabilizing less favorable intermediates



OF ABZYMES Anti- idiotypic approach: from enzymes to abzymes




Antibodies with catalytic activities were isolated from sera of patients with different diseases. The first natural abzymes were obtained by means of antibody purification from human serum. Antibodies with protease activity against vasoactif intestinal peptide (VIP) were first isolated in the serum of patients with asthma. This VIP-ase activity was also shown to be present on proteins, that are monoclonal human light chains found in urine of patients with multiple myeloma. Other protease activities were charaterized for cleaving of throglobulin in the serum of patients with Hashimoto thyroiditis, or for hydrolyzing factor VIII in hemophilia patients infused with homologous factor VIII . DNA hydrolyzing autoantibodies were also isolated from the sera of patients with systemic lupus erythematosus or rheumatoid arthritis .


The idea to produce metalloenzymes or hemoenzymes was to generate antibodies able to cleave stable chemical bonds or to catalyze peroxidase-like reactions. In 1989, an antibody catalyzing the hydrolysis of a Glycine-Phenylalanine bond was obtained by using as the antigen an hapten that not only induce the selective recognition of the Gly-Phe sequence, but also induce the generation of residues able to complex a metal ion. When complexed with zinc, this antibody exhibits a good catalytic activity. Hemoabzymes obtained are able to catalyze peroxidase-like activities and could be very interesting tools for the enantioselective oxidation of molecules.

APPLICATIONS OF ABZYMES Industrial applications 1.Great potential in the pharmaceutical industries.
2. Detoxification of cocaine.

3. Specific targeting of cancer cells unique determinants, called tumor cell antigens, on their surface that are lacking in normal cells. 4. One application could concern the use of hydrolytic properties of abzymes to activate prodrugs. By targeting this activity in the vicinity to tumor cells, prodrugs could be transformed into cytotoxic compounds directly on tumor cells. This anti-cancer therapy is designed as Antibody-Directed Abzyme Prodrug Therapy (ADAPT)

5. Inactivate viruses. 6. High abzyme activity is observed in blood of pregnant women. 7. In Israel Advanced Biotech is producing catalytic antibodies for the treatment of gram-negative sepsis, targeting the endotoxin LPS. 8. Finally, all researches aimed to produce antibodies with a sequence-specific protease activity could open new ways for anti-virus therapy and for the conception of new vaccines.

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