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Scientists Develop Catalytic Antibody With Comparable Efficiency And Of Broader Use Than Natural Enzyme

Date:
December 23, 1997
Source:
Scripps Research Institute
Summary:
For the first time, scientists at The Scripps Research Institute (TSRI) have developed a catalytic antibody with an efficiency and mechanism equal to that of a natural enzyme essential to life.
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For the first time, scientists at The Scripps Research Institute (TSRI) have developed a catalytic antibody with an efficiency and mechanism equal to that of a natural enzyme essential to life. According to Richard Lerner, M.D., TSRI President and the study's author, "We have simulated an important enzyme via an antibody, while broadening its specificity. In addition, this will be the first commercially available catalytic antibody." The scientists believe that it will have numerous applications in industrial synthesis, including the synthesis of some of the most important anticancer compounds.

The work, "Immune Versus Natural Selection: Antibody Aldolases with Enzymic Rates but Broader Scope" appears in the Dec. 18 issue of Science. Other authors include Carlos F. Barbas, III, Andreas Heine, Guofu Zhong, Torsten Hoffmann, Svetlana Gramatikova, Robert Bjornestedt, Benjamin List, James Anderson, Enrico A. Stura, and Ian A. Wilson. The researchers are members of The Skaggs Institute for Chemical Biology and the Department of Molecular Biology at TSRI.

The scientists compared aldolases that use the same chemical mechanism but differ in their origin. One is a naturally-evolved enzyme and the other, a catalytic antibody developed by reactive immunization. The work solves the dilemma of whether the immune system is capable of creating efficient catalysts by altering its selection criteria from simple binding to function.

While antibodies generally bind non-covalently with their substrates, the technique of reactive immunization enables catalytic antibodies to react with antigens, allowing the catalysis of chemical reactions previously thought to be impossible. In this case, the antibodies catalyze the aldol reaction, an important carbon-carbon bond-forming reaction and one of the most widely used in making pharmaceuticals, and diagnostic and imaging materials.

Because the natural catalysts are too highly restricted in the substrates they use to be of general use to chemists, the scientists also aimed to generate antibodies that are capable of catalyzing reactions with a greater range of substrates than the enzymes that exist in nature.

By moving from the creation of antibodies using the principle of transition-state stabilization to reactive immunization, the scientists have created an antibody that behaves in similar manner to the natural enzyme with regard to its reaction chemistry. In so doing, they have programmed a set of binding pockets to interact with substrates in much the same way as the natural catalyst. According to Lerner, this directly addresses the issue of whether proteins can be made with comparable catalytic efficiency as enzymes when each uses a similar mechanism. He commented, "While we would not suggest that catalytic antibodies will ultimately prove to be as efficient as all enzymes, this work demonstrates that we can develop an antibody whose efficiency can approximate that of a natural enzyme whose function is essential to all life."

Further, this study provides insights into the evolution of metabolic enzymes that relate to theories of the origins of life.

Funding for the study was provided by the National Institutes of Health and The Skaggs Institute for Chemical Biology.


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The above post is reprinted from materials provided by Scripps Research Institute. Note: Materials may be edited for content and length.


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Scripps Research Institute. "Scientists Develop Catalytic Antibody With Comparable Efficiency And Of Broader Use Than Natural Enzyme." ScienceDaily. ScienceDaily, 23 December 1997. <www.sciencedaily.com/releases/1997/12/971223070617.htm>.
Scripps Research Institute. (1997, December 23). Scientists Develop Catalytic Antibody With Comparable Efficiency And Of Broader Use Than Natural Enzyme. ScienceDaily. Retrieved September 2, 2015 from www.sciencedaily.com/releases/1997/12/971223070617.htm
Scripps Research Institute. "Scientists Develop Catalytic Antibody With Comparable Efficiency And Of Broader Use Than Natural Enzyme." ScienceDaily. www.sciencedaily.com/releases/1997/12/971223070617.htm (accessed September 2, 2015).

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