2. ā¢ Introduction
ā¢ Ideal characteristics of synzymes
ā¢ Mechanism of Enzyme catalysis
ā¢ Design approaches for synzymes:
ā¢ Cyclodextrine
ā¢ cyclophane
ā¢ Reaction catalysis by synzymes:
ā¢ Palladium based catalysis
ā¢ Multiple Chain Reaction
CONTENT TO BE STUDY...
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3. ā¢ Artificial enzymes may be defined as the synthetic, organic molecule
prepared to recreate/mimic the active site of an enzyme.
ā¢ They have a molecular weight less than 2000 Dalton.
ā¢ They have the ability to stabilize at high temperatures.
ā¢ They are also known as synzymes or enzyme mimics.
ā¢ These catalytic groups are usually chosen to mimic the amino acid
residues known to be involved in the enzyme catalysed reaction.
INTRODUCTION
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4. ā¢ Hydrophobic binding site for the substrate.
ā¢ Hydrogen bonding and/or electrostatic binding sites
complementary to the substrate.
ā¢ Catalytic group attached to the model.
ā¢ Rigid structure model.
ā¢ Water soluble and catalytically active under physiological
conditions.
ā¢ Reversible, non-covalent binding with the release slower than the
binding.
IDEAL CHARACTERISTICS OF SYNZYMES
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5. ā¢ Enzymes are molecule
complementary to the
transition states of the
reaction they catalyze.
It should result in strain
at the scissile bond (-
73.2 kJ/mol for the
transition state of the
deamination of ATP).
E + S ES P + E
k1/k2 = k12
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MECHANISM OF ENZYME
CATALYSIS
k1
k2
kcat
6. DESIGN APPROACH
C Y C L O D E X T R I N
ā¢ To mimic ribonuclease A enzyme, two imidazole rings
were attached to the primary face of b-cyclodextrin as
depicted below in figure 1. This mimic 7 catalyses the
hydrolysis of the cyclic phosphate 8 and shows greater
than 99:1 selectivity for 9.
ā¢ Positioning of the imidazole groups on the ring of the
b-cyclodextrin was found to be crucial. Only when the
imidazole groups were attached to adjacent sugars was
a single product 9 detected. This regioisomer of b-
cyclodextrin provids the fastest rate of hydrolysis and
displayed the strongest binding to the substrate 8.
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7. DESIGN APPROACH
ā¢ Diederichās pyruvate oxidase mimic employs
two co-factors Thiamine pyrophosphate and
Flavin to water or alcohols to carboxylic acids or
esters respectively by simple thiazolium ions in
the presence of flavin.
ā¢ They bind to the site with both the flavin and
thiazolium groups attached in covalent fashion
(Figure 3).
C Y C L O P H A N E
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8. REACTION CATALYSIS
ā¢ Different types of reaction were being catalyzed
by palladium enzymes:
ā¢ Negishi coupling reaction
ā¢ Heck reaction
ā¢ Stille reaction, etc.
P A L L A D I U M C A T A L Y S I S
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9. REACTION CATALYSIS
ā¢ The two starting materials in the reactant path bind
to that site and are converted by the
imidazolidinone to an intermediate product. This
intermediate product then diffuses to the second
star polymer designed to immobilize the second
catalyst, a pyrrolidine derivative. There, it is
converted to the final product through
simultaneous catalysis by the pyrrolidine and a
third catalyst, this one in solution. When all three
catalysts were present, 90% of the starting material
was converted to product, showing that a
ācascadeā of all reaction steps had occurred.
M U L T I P L E S T E P R E A C T I O N
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