Mar 6, 2008

Abzymes

Abzymes

Upps Enzyme Antibody Abzymes confuses me….

The binding of an antibody to its antigen is similar in many ways to the binding of an enzyme to its substrate. In both cases the binding involves weak, noncovalent interactions and exhibits high specificity and often high affinity. What distinguishes an antibody-antigen interaction from an enzyme-substrate interaction is that the antibody does not alter the antigen, whereas the enzyme catalyzes a chemical change in its substrate. However, like enzymes, antibodies of appropriate specificity can stabilize the transition state of a bound substrate, thus reducing the activation energy for chemical modification of the substrate.

Discovery…

The similarities between antigen-antibody interactions and enzyme-substrate interactions raised the question of whether some antibodies could behave like enzymes and catalyze chemical reactions. To investigate this possibility, a hapten-carrier complex was synthesized in which the hapten structurally resembled the transition state of an ester undergoing hydrolysis. Spleen cells from mice immunized with this transition state analogue were fused with myeloma cells to generate monoclonal antihapten monoclonal antibodies. When these monoclonal antibodies were incubated with an ester substrate, some of them accelerated hydrolysis by about 1000-fold; that is, they acted like the enzyme that normally catalyzes the substrate’s hydrolysis. The catalytic activity of these antibodies was highly specific; that is, they hydrolyzed only esters whose transition-state structure closely resembled the transition state analogue used as a hapten in the immunizing conjugate. These catalytic antibodies have been called abzymes in reference to their dual role as antibody and enzyme.

What’s in Research??

A central goal of catalytic antibody research is the derivation of a battery of abzymes that cut peptide bonds at specific amino acid residues, much as restriction enzymes cut DNA at specific sites. Such abzymes would be invaluable tools in the structural and functional analysis of proteins. Additionally, it may be possible to generate abzymes with the ability to dissolve blood clots or to cleave viral glycoproteins at specific sites, thus blocking viral infectivity. Unfortunately, catalytic antibodies that cleave the peptide bonds of proteins have been exceedingly difficult to derive. Much of the research currently being pursued in this field is devoted to the solution of this important but difficult problem.