catalytic antibodies
TRANSCRIPT
ABZYMES
Arushe Tickoo
M. Tech IBT
ABZYMES
Catalytic monoclonal antibodies
AB : Ab (Antibodies)
ZYMES(Enzymes)
Antibodies + Enzymes
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
• 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
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.
• 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
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 ex
perimental animals.
– If the molecule is a transition state analog, then the
antibodies that are pro duced to bind to this molecule
will function as enzyme towards the substrate of this
reac tion.
– 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).
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).
• 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.
Applications
• Treatment of cancer
• Abzymes in treatment of HIV
• Drug Detoxification
• Abzymes against weight gain
• Antibody directed enzyme prodrug
therapy
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.
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.
ANTIBODY DIRECTED ENZYME PRODRUG THERAPY
• 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.
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
