Origins of Sugars in the Prebiotic World

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Origins of Sugars in the Prebiotic World

• One theory the formose reaction (discovered by
  Butterow in 1861)
• Mechanism?

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Cont
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• Today, similar reactions are catalyzed by
  thiazolium, e.g., Vitamin B1 (TPP), another
  cofactor
• Cf Exp. 7 Benzoin condensation
• e.g.

Mechanism? Uses thiazolium
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• We have seen how the intermediacy of the
  resonance-stablized oxonium ion accounts for
  facile substitution at the anomeric centre of a
  sugar
• What about nitrogen nucleophiles?
• Many examples
• Could this process have occurred in the prebiotic
  world?

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• Reaction of an oxonium ion with a nitrogenous
  base NUCLEOSIDES!
• Nucleosides are quite stable
• Weaker anomeric effect Nlt O lt Cl (low
  electronegativity of N)
• N lone pair in aromatic ring ? hard to protonate

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1)
Anomeric effect Cl gt O gt N (remember the
glycosyl chloride prefers Cl axial
2)
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• These effects stabilize the nucleoside making its
  formation possible in the pre-biotic soup
• Thermodynamics are reasonably balanced
• However, the reaction is reversible
• e.g. deamination of DNA occurs 10,000x/day/cell
  in vivo
• Deamination is due to spontaneous hydrolysis by
  damage of DNA by environmental factors
• Principle of microscopic reversibility
  spontaneous reaction occurs via the oxonium ion

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Ribonucleosides Deoxyribonucleosides

• Ribonucleosides
• Contain ribose found in RNA
• Deoxyribonucleosides
• Contain 2-deoxyribose, found in DNA

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Ribonucleosides
Deoxyribonucleosides
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• Important things to Note
• Numbering system
• The base is numbered first (1,2, etc), then the
  sugar (1, 2, etc)
• Thymine (5-methyl uracil) replaces uracil in DNA
• Confusing letter codes
• A represents adenine, the base
• A also represents adenosine, the nucleoside
• A also represents deoxyadenosine (i.e., in DNA
  sequencing, where d is often omitted)
• A can also represent alanine, the amino acid

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• Nucleoside phoshphate ? nucleotide
• In the modern world, enzymes (kinases) attach
  phosphate groups

In the pre-RNA world, how might this happen?
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Observation

• Surprisingly easy to attach phosphate without
  needing an enzyme
• One hypothesis cyclo-triphosphate (explains
  preference for triphosphate

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• If correct, this indicates a central role for
  triphosphates of nucleosides (NTPs) in early
  evolution of RNA (i.e., development of the RNA
  world)
• NTPs central to modern cellular biology