Enzyme Mimics (Artificial Enzymes)

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Enzyme Mimics (Artificial Enzymes)

• Reproduce the enzymes 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
• Kogas crown ethers

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• 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

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Cyclodextrins
?-cyclodextrin

• 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

cavity
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• Research on cyclodextrin started in the 1930s
• Very expensive thought to be toxic
• 1970s ? 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)

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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

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• Can use similar chemistry to a condensation
  reaction

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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

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An Artificial Transaminase (Coenzyme Bound)

• Rates
• phenylpyruvic acid 100x faster than pyruvic
  acid
• increase hydrophobicity ? further rate increase
  (15 000x)

Compete for CD
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Other Coenzyme mimics

• Benzoin condensation with thiazolium ion mimic
  (recall exp. 7, dilantin synthesis)

(note the use of a ? cyclodextrin)
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• Some more mimics

NADH mimic
Flavin mimic
Dimeric
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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

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Example Hydrolysis of ATP (mimics ATPase)
Binding via electrostatic forces H-bonding
cryptand
Hydrolysis of ATP ?500x
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Catalytic Antibodies

• Exploit the excellent binding abilities that
  antibodies possess
• Molecular recognition
• Construct a transition state analogue ? screen
  for antibodies against this molecule

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Make a TS mimic
Reaction to Study
Mimic
Mimics tetrahedral-like transition state
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Screen for antibodies against your TS analogue
Catalyzes rxn by forcing substrates into a
TS-like geometry (i.e. binding proximity
effects)
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• Catalytic antibodies are good for simple
  reactions, but are limited by
• Accuracy ? transition state analogue
• Screening
• Applications detoxification of cocaine