Enzyme Mimics (Artificial Enzymes) Reproduce the enzyme’s function Mimic a chemical reaction...
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Transcript of Enzyme Mimics (Artificial Enzymes) Reproduce the enzyme’s function Mimic a chemical reaction...
Enzyme Mimics (Artificial Enzymes)
• Reproduce the enzyme’s function• Mimic a chemical reaction
– Chemical transformation (covalent bonds)
&/or• Molecular recognition
– Mimic binding (H-bonding, hydrophobic, ionic, etc)
• We have already seen two biomimetic catalytic systems:– Organocatalysis with proline– Koga’s crown ethers
• Things to consider:– Needs to be an initial binding step– Size: important for binding & release of product– To be truly catalytic, there needs to be turnover
• Several examples of mimics found in research and industry:– We will look at:
• Cyclodextrins• Cryptands• Catalytic antibodies
Cyclodextrins
• 6 (), 7 (), or 8 () glucose units
• Hydrophobic cavity• Stable & water soluble• Tunable (modify to
change properties)• Several examples of its
use for biomimetic catalysis:– Condensation rxns– Redox chemistry– etc
-cyclodextrin
cavity
• Research on cyclodextrin started in the 1930’s– Very expensive & thought to be toxic
• 1970’s → non-toxic, but still $2000/kg• Now → cheap! → 1000 tons/y• Several industrial applications
– Self-tanning lotions, laundry drier sheets, flavorings, etc.– Produced by environmentally-friendly technologies & renewable
materials • Starch → cyclodextrin (action of CTGase)
Mimic of Ribonuclease A
• Hydrolyses RNA using two His residues for acid/base catalysis (no general agreement on how)
• Mimic the Rib A system by attaching imidazole groups on cyclodextrin
• Can use similar chemistry to a condensation reaction:
An Artificial Transaminase
• Recall transamination of AAs with pyridoxal phosphate (PLP)
• Use cyclodextrin to perform the same chemistry with a covalent linkage to a PLP derivative
N
OH
OH
O P
O
O
OOH
O
O
OH
O
NH2
N
OH
NH2
O P
O
O
O
PLP pyruvic acidalanine
++
An Artificial Transaminase (Coenzyme Bound)
+
Compete for CD
Rates:
• phenylpyruvic acid 100x faster than pyruvic acid
• increase hydrophobicity → further rate increase (15 000x)
O
O
OH
Other Coenzyme mimics
Benzoin condensation with thiazolium ion mimic (recall exp. 7, dilantin synthesis):
(note the use of a cyclodextrin)
Some more mimics
NADH mimic Flavin mimic
Dimeric
Cryptands
• Cryptands are multi-dendate ligands that bind cations (“buried”)– Similar to a crown ether, but usually more selective and they
exhibit stronger binding– Nobel Prize 1987
cryptand
Binding via electrostatic forces & H-bonding
Example: Hydrolysis of ATP (mimics ATPase)
Hydrolysis of ATP 500x
Catalytic Antibodies
• Exploit the excellent binding abilities that antibodies possess– Molecular recognition
• Construct a transition state analogue → screen for antibodies against this molecule
O2NO
OMeH
OH
O2NO
OH
HO
H
O
+
Make a TS mimic
O2NP
O
ORMimic:
Reaction to Study:
Mimics tetrahedral-like transition state
O2NP
O
ORScreen for
antibodies against your TS analogue
O2NO
OMeH
OH O2N
O
OH
+
Catalyzes rxn by forcing substrates into a TS-like geometry (i.e. binding & proximity effects)
• Catalytic antibodies are good for simple reactions, but are limited by:– Accuracy → transition state analogue– Screening
• Applications: detoxification of cocaine