BIOTECHNOLOGY - Inshyna N.M. - 2009

CHAPTER 2. PROTEIN ENGINEERING

Abzymes — Catalytic Antibodies

In 1986, R.A. Lerner and P.G. Schultz discovered that antibody molecules can exhibit catalytic activity. Abzymes have been detected in The Human Body, with their appearance associated with certain common diseases. It was found that severe forms of hemophilia can result from The formation of autoimmune catalytic Antibodies that cleave factor VIII (a Blood clotting protein factor). In hepatitis B, antibodies possessing RNase activity (catalyzing RNA Cleavage) have been identified.

A new direction in Protein Engineering has emerged, focused on the artificial design of Enzymes based on immunoglobulin polypeptide chains. Abzymes engineered through protein engineering Methods can drive reactions not catalyzed by natural enzymes. This approach is utilized for the selective activation of toxic compound precursors during Cancer Chemotherapy.

Abzymes capable of hydrolyzing toxic organophosphorus compounds have been developed. This enables the application of abzymes in reactions that proceed via the formation of highly reactive intermediates, such as carbocations, 1,3-dipoles, and triplet diradicals. It has been established that abzymes can mediate amide synthesis and catalyze stereospecific cyclization reactions. Such Examples highlight the immense potential of abzymes as artificial biocatalysts for Chemical Reactions.