ABZYMES
SHIJINA.A
BCH 10-05- 04
S2 MSc BIOCHEMISTRY
Introduction
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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.
 Antibodies have been 1st characterized as proteins
produced by the IS for binding with molecules called
antigens.
 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
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In 1986 , the 1st monoclonal catalytic antibodies
termed abzymes against a chemically stable analog
of the transition state of a reaction were obtained
Abzymes are catalytic antibodies having structural
complementarity for the transition state of an
enzyme catalyzed reaction.
They bind strongly to the transition state with high
association constant, enhancing the reaction rate .
Abzymes reduce rotational entropy .
Sources of Abzymes
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Abzymes are usually artificial constructs.
They also obtained from human and animal serum.
Found in normal humans and ii patients with
autoimmune diseases.
These are capable of hydrolyzing proteins, DNA,
RNA, polysaccharides etc
Protabzymes and DNA Abzymes
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Natural abzymes with proteolytic activity are called
Protabzymes .e.g.: hydrolysis of specific proteins in
patients with autoimmune diseases such as
bronchial Asthma ,multiple sclerosis.
DNA hydrolyzing activity are called DNA abzymes.
The pathogenic role of DNA abzymes is not quite
clear. However they act as a powerful regulator of
apoptosis.
Production of abzymes
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Antibody molecules are produced by the immune
system to bind and neutralize foreign substances
called antigens
Foreign proteins of bacteria , viruses and some
chemical molecules called haptens , act as antigens .
Transition state analogs are molecules which are
more stable than the transition state itself , but they
mimic its 3D structure .
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If injected into the blood stream of an animal ,
transition state analogs act as haptens and elicit
antibody production.
Abs are isolated from the serum of the animal and
used as abzymes .
Theoretically ,if the Ab binds to a transition state
molecule, it may be expected to catalyze a
corresponding chemical reaction by forcing
substrates into transition state geometry.
Transition
state
Substrate
Pdt
mice
Transition
state analog
(act as Ag)
Ab complementary
to transition state
Examples for abzymes
1.
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Hydrolysis of hydroxy ester by abzymes
Hydroxy ester forms a cyclic intermediate
during hydrolysis.
Cyclic phosphonate ester is the structural analog
of the cyclic intermediate.
This analog is used as an antigen to elicit
antibodies.
These antibodies bind the cyclic intermediate ,
increasing the reaction rate .
Hydroxy ester
Cyclic intermediate
δ-lactone
phenol
Anti –cyclic intermediate antibody
(Abzymes)
Cyclic phosphonate ester (antigen)
,mimic cyclic intermediate
2.
Hydrolysis of ester by abzymes
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Ester forms a tetrahedral intermediate during
hydrolysis
The phosphate analog of ester mimic this intermediate,
used as antigen to elicit antibodies.
These antibodies recognize and bind to tetrahedral
intermediate and stabilize it resulting in rate
acceleration.
 Biosynthesis
of Heme
• It involves introduction of Fe2+ into
protophorphyrine by ferrochelatase.
• This process is called metallation
• Metallation involves the distortation of pyrole ring
by 36ºto create a bent transition state
• This state is apt for the entry Fe2+
• Methyl mesoporphyrin , an analog of the bent
transition state , is used as antigen to elicit
abzymes.
• These abzymes bind the bent transition state and
distorts the porphyrin facilitating metallation rate
2500fold higher
Reactions catalyzed by Abzymes
1.
2.
3.
4.
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6.
7.
8.
9.
Amide hydrolysis
Trans- Esterification
photo cleavage
Photodimerization
Decarboxylation
Oxidation
Cyclization
Reduction of diketone
Hydrolysis of enol ethers
Applications
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Synthesis of simple organic molecules
 Drug development
 Treat Cancer
 Treat allergy
 treat viral and bacterial infection
Reference
 Enzymology
–T. Devasena
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