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Enzyme Mimics (Artificial Enzymes)

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:

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Enzyme Mimics (Artificial Enzymes)

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  1. 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

  2. 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

  3. 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

  4. 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)

  5. 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

  6. Can use similar chemistry to a condensation reaction:

  7. 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

  8. An Artificial Transaminase (Coenzyme Bound) • Rates: • phenylpyruvic acid 100x faster than pyruvic acid • increase hydrophobicity → further rate increase (15 000x) Compete for CD

  9. Other Coenzyme mimics Benzoin condensation with thiazolium ion mimic (recall exp. 7, dilantin synthesis): (note the use of a  cyclodextrin)

  10. Some more mimics NADH mimic Flavin mimic Dimeric

  11. 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

  12. Example: Hydrolysis of ATP (mimics ATPase) Binding via electrostatic forces & H-bonding cryptand Hydrolysis of ATP 500x

  13. Catalytic Antibodies • Exploit the excellent binding abilities that antibodies possess • Molecular recognition • Construct a transition state analogue → screen for antibodies against this molecule

  14. Reaction to Study: Make a TS mimic Mimic: Mimics tetrahedral-like transition state

  15. Screen for antibodies against your TS analogue Catalyzes rxn by forcing substrates into a TS-like geometry (i.e. binding & proximity effects)

  16. Catalytic antibodies are good for simple reactions, but are limited by: • Accuracy → transition state analogue • Screening • Applications: detoxification of cocaine

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