An abzyme (from antibody and enzyme), also called catmab (from catalytic monoclonal Archived from the original (PDF) on Retrieved The possibility of the induction of catalytic antibod ies (abzymes) was initially suggested by Pauling in ; he noted similar features between mechanisms of . Catalytic antibodies (abzymes) like enzymes process their substrates through a Michaelis complex in which the chemical transformation occurs, followed by.
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The importance of generating antibodies to catalyse specific reactions was discussed. The synthesis of transition state analogues, raising antibodies to them, as well as utilising them in a variety of catalytic reactions have been highlighted in this review. Amide hydrolysis by. PDF | This review summarizes literature data on natural abzymes. Peculiar features of their functioning and substrate specificity are considered in comparison. XI - Abzymes - A Challenge for the Medical Biotechnology and Public Health - I. Getov, Perspectives for abzyme technology as a new branch of medical and.
Abzymes are usually artificial constructs, but natural abzymes are also known. Enzymes act by binding the transition state of a reactant better than the ground state. 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. Obviously, its structure mirrors the structure and electrostatic properties of the sulphoxide transition state.
Also the scFv phage abzymes elicited by different antigens displayed different catalytic activities. This study might be helpful for new haptens or antigens design to optimize the abzymes with high binding activities and might also provide a novel scheme for GPX mimic candidates for drug development.
Introduction Glutathione peroxidase GPX is a key peroxidase for protecting biomolecules from oxidative damage by eliminating hydrogen peroxide and lipid peroxide from the body and further blocking the injury of reactive oxygen free radicals in biological organisms. Selenocysteine is located in the active center of the GPX, 1,2 which could also reflect the selenium level of the body.
Furthermore, selenium, a structural part of a large group of selenoproteins is necessary for proper functioning of the body. For example, when hemolyzates from erythrocytes of selenium-deficient rats were incubated in vitro in the presence of ascorbate or H 2 O 2 , added glutathione failed to protect the hemoglobin from oxidative damage.
This occurred because the erythrocytes were practically devoid of glutathione-peroxidase activity.
Many of the nutritional effects of selenium can be explained by its role in glutathione peroxidase. Extensive research has been carried out to design and synthesize small organoselenium compounds as functional mimics of GPX. While the catalytic mechanism of the native enzyme itself is poorly understood, the synthetic mimics follow different catalytic pathways depending upon the structures and reactivities of various intermediates formed in the catalytic cycle.
In theory, humanized GPX should be one of the most effective anti-oxidation drugs. Also, it could be a shortcut that only a few weeks might be taken for an antibody affinity maturation as the incomparable diversity of the abzyme, while millions of years might be taken for a native enzyme evolution.
Due to strong binding affinity and high specificity in antibodies against antigens, antibody-catalyzed reactions proceed in a highly regio- and stereo-selective manner, thus the development of new synthetic methods for organic synthesis provides a clear advantage.
However, due to the nature of the binding of monoclonal antibody binding to its substrate, the substrate specificity of antibody catalytic reaction is very limited.
Therefore, the practical application of catalytic antibodies in organic synthesis requires to expand its substrate specificity. In order to study the catalytic mechanism and develop novel pharmaceutical lead compounds, we have explored several mimic GPXs producing high activity according to the murine abzymes. As an exogenous protein, the murine GPX enzyme could not be applied in the clinic. It is imperative to develop the humanized GPX abzyme. The preparation of an abzyme depends on the hapten design.
The structure of an ideal hapten candidate should be as close as possible to that of the transition-state analog in the actual reaction, at the same time, as far as possible be different from that of the product and the substrate, which could minimize the inhibition to introduce the active residues involved in the reaction.
In vitro, there're usually a few approaches utilized to develop humanized hapten-specific antibodies: humanization of a murine antibody, biopanning of a human phage antibody library or a yeast display human scFv library, or eliciting antibodies with transgenic animals. DNA shuffling is a new technique for the directed molecular evolution.
In recent years, the DNA shuffling technique has been widely applied with broad prospects and great application value in the area of biological engineering. An esterase-like activity of the antibody containing site?
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