Catalytic antibodies

Introduction, History of abzymes, Mechanism of action and applications

1. A BZYMES Arushe Tickoo M . Tech IBT

2. ABZYMES Catalytic monoclonal antibodies AB : Ab ( Antibodies) ZYMES (Enzymes) Antibodies + Enzymes

3. Introduction An abzyme (from antibody and enzyme), also called catmab (from catalytic monoclonal antibody), and most often called catalytic antibody, is a monoclonal antibody with catalytic activity . A single molecule of an antibody-enzyme, or abzyme , is capable of catalyzing the destruction of thousands of target molecules

4. Abzymes are usually raised in lab animals immunized against synthetic haptans , but some natural abzymes can be found in normal humans (Intestinal peptide autoantibodies) and in patients with autoimmune diseases where they can bind to and hydrolyze DNA. One basic difference between antibodies and enzymes is that the former binds the complementary structure in its ground state while enzymes bind in high energy state

5. History In 1994, Peter G. Schultz and Richard A. Lerner received the prestigious Wolf Prize for developing catalytic antibodies . The possibility of catalyzing a reaction by means of an antibody which binds the transition state was first suggested by William P. Jencks in 1969.

6. Antibodies and enzymes share the ability to bind with compounds with great specificity and high affinity. This property has been exploited in the development of antibodies with catalytic activity. 1995-2011: Dr. Paul publishes first example of hydrolysis of HIV coat protein by an abzyme

7. Principle The production of the abzymes is based on the following two principles: 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.

8. If th e 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 ( Haptens are small molecules that elicit an immune response only when attached to a large carrier such as a protein).

9. Mechanism of Action Enzymes function by lowering the activation energy of the transition state of a chemical reaction, thereby enabling the formation of an otherwise less-favorable molecular intermediate between the reactant(s) and the product(s ).

10. If an antibody is developed to bind to a molecule that's structurally and electronically similar to the transition state of a given chemical reaction, the developed antibody will bind to, and stabilize, the transition state, just like a natural enzyme, lowering the activation energy of the reaction, and thus catalyzing the reaction. By raising an antibody to bind to a stable transition-state analog, a new and unique type of enzyme is produced.

11. Applications Treatment of cancer Abzymes in treatment of HIV Drug Detoxification Abzymes against weight gain Antibody directed enzyme prodrug therapy

12. CATALYTIC ANTIBODIES IN HIV TREATMENT CD4 binding site on surface HIV gp120 molecules, the mostly-unchanging binding site of the virus that reacts with host cell receptors. The abzyme does more than bind to the site, it catalytically destroys the site, rendering the virus inert, and then can attack other HIV viruses. A single abzyme molecule can destroy thousands of HIV viruses.

13. ABZYMES IN DRUG DETOXIFICATION Cocaine taken by a person(in form of drug or stimulant) goes to brain via blood circulation(crossing the blood brain barrier) and may cause damage to brain. To overcome it cocaine transition state can be used as vaccines. When given to patient, antibodies will be generated against cocaine transition state which will detoxify cocaine if patient consumes it in future.

14. ANTIBODY DIRECTED ENZYME PRODRUG THERAPY

15. In some cases unwanted protein- protein interaction can also be responsible for various problems or abnormalities in body. So to overcome it, catalytic antibodies can be used which binds to interacting domains of these proteins and prevent unwanted protein protein interactions.

16. Abzymes also plays important role in maintaining proper body weight through dedradation of ligands which binds to a specific receptor and show physiological effect.( eg - growth hormone receptors and LDL receptors). ABZYMES AGAINST WEIGHT GAIN AND CONTROLLING OBESITY