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The below mentioned article provides a study note on abzymes.
Abzymes (from antibody and enzyme) are antibodies that catalyze specific chemical reactions i.e., function as enzymes. Abzymes are also called as catmab (from catalytic monoclonal antibody). Abzymes are usually artificial constructs, but natural abzymes are also known.
The production of the abzymes is based on the following two principles:
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1. Enzymes act by binding the transition state of a reactant better than the ground state.
2. Antibodies which bind to specific small molecules can be produced by coupling this small molecule to a protein carrier and using this protein for immunizing experimental animals.
If this small molecule is a transition state analog, then the antibodies that are produced to bind to this molecule will function as enzyme towards the substrate of this reaction. Abzymes are selected from monoclonal antibodies produced by immunizing mice with haptens that mimic the transition state of enzyme catalyzed reactions. For example, 28B4 abzyme catalyzes periodate oxidation of p-nitrotoulene methyl sulphide to sulphoxide, where electrons from the sulfur atom are transferred to the more electronegative oxygen atom.
The rate of this reaction is promoted by enzyme catalysts that stabilize the transition state of this reaction, thereby decreasing the activation energy and allowing for more rapid conversion of substrate to product.
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In this case, the transition state is believed to involve a transient positive charge on the sulfur atom and a double negative charge on the periodate ion as shown below:
In order to produce abzymes complementary in structure to this transition state, mice were immunized with an aminophosphonic acid hapten as depicted above. Obviously, its structure mirrors the structure and electrostatic properties of the sulphoxide transition state. Of the hapten-binding monoclonal antibodies produced with this hapten, many were found to catalyze sulphide oxidation but with a wide range of binding affinities and catalytic efficiencies. Abzyme 28B4 binds hapten with high affinity and exhibits a corresponding high degree of catalytic efficiency.
Abzymes have proven to be very important tools in Biotechnology and Medical Pathology in combating dreaded human diseases like AIDS, Cancer etc. One of the promising directions in this field consists of the production of abzymes catalyzing rapid cleavage of hazardous compounds, including toxins and drugs such as cocaine.
