Could the Primordial gene have been a peptide

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Could the Primordial gene have been a peptide?
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The Central Dogma
DNA RNA Protein
Genetic information
Function
Genetic information (transfer) ( Function)
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The Origin of Life on Earth
?
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The Miller ExperimentPrimordial Soup
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Origin of LifePrebiotic Synthesis

• Amino Acids Quite readily (Miller)
• Nucleobases Quite readily (Oro)
• Ribose With great difficulty (Eschenmoser and
  others)

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Peptide Nucleic Acids (PNA)
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DNA Recognition
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Triple Helix
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Triple Helix
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PNA Design
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PNA Properties Chemistry

• PNAs are achiral, charge neutral and generally
  hydrophilic, reasonably water soluble
• PNAs are chemically and biologically stable
• PNA oligomers are synthesized by conventional
  solid phase peptide chemistry Fmoc/tBoc

Egholm et al.J Am Chem Soc 1992, 114
9677-9678.Christensen et al. J Pept Sci 1995, 1
185-83. Demidov et al Biochem Pharmacol 1994, 48
1310-1313.
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PNA Properties Hybridization

• Hybrid thermal stability
• PNA-NA ionic strength indepedent
• PNA-PNA gt PNA-RNA gt PNA-DNA gt DNA-DNA
• However strong base composition dependence
• purine-PNA gtgt pyrimidine-PNA, but
• homopyrimidine-PNA very stable PNA2-NA triplexes

Tmpred 20.79 0.83 x TmnnDNA -26.13 x fpyr
0.44 x length
Egholm et al. Nature 1993, 365 566-568. Jensen
et al. Biochemistry 1997, 36 5072-5077.Giesen et
al. Nucleic Acids Res 1998, 26 5004-5006.
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PNA Structure
Rasmussen, Kastrup, Nielsen, Nielsen, Nielsen Nat
Struct Biol 1997, 4 98-101.
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The Miller ExperimentPrimordial Soup

• Amino acids
• DNA bases
• Not ribose
• PNA units

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Origin of LifePrebiotic Synthesis

• Amino Acids Quite readily (Miller)
• Nucleobases Quite readily (Oro)
• Ribose With great difficulty (Eschenmoser and
  others)
• PNA Possible (Miller)

Nelson KE, Levy M, Miller SL Peptide nucleic
acids rather than RNA may have been the first
genetic molecule. Proc Natl Acad Sci U S A 2000,
97 3868-3871
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Peptide Nucleic Acids (PNA) as Protogenes
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PNA backbone structure
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Prebiotic Origin of Life

• Prebiotic building block synthesis
• Prebiotic oligomer synthesis
• Genetic inheritance
• Homochirality

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Peptide Nucleic Acids (PNA) as a Model for an
Achiral Prebiotic Genetic Material
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Origin of Life PNA RNA
Böhler C, Nielsen PE, Orgel LE Nature 1995, 376
578-581.
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Peptide Nucleic Acids (PNA) as a Model for an
Achiral Prebiotic Genetic Material
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PNA Lactam Formation
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PNA Directed PNA Synthesis
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PNA Directed PNA Synthesis
No template
dC10 template
PNA C10 template
Me-Imidazole
Imidazole
Böhler, Nielsen Orgel (1995) Nature 376, 578
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DNA Directed PNA-DNA Ligation
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PNA Directed PNA-PNA Ligation
-CH3OH
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Induced Chirality in PNA Helices
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CD Spectra of PNA Helices
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Enantio Selective PNA-DNA ligation
Kozlov, Orgel, Nielsen Angew Chem , 2000, 39
4292
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Enantio Selective PNA-DNA ligation
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Enantio selective PNA-DNA ligation
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Acknowledgements
The Salk Institute Leslie Orgel Christof
Böhler Jürgen Schmidt Igor Koslov
University of Copenhagen Anjana Sen
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DNA Directed PNA-DNA Ligation
Koppitz, Nielsen Orgel (1998) J. Amer. Chem.
Soc. 120, 4563
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The Assymmetry of PNA-DNA Duplexes
PNA-DNA duplex
Pu AGGTAACGAG Py CTCGTTACCT
Tmpred 20.79 0.83 x TmnnDNA -26.13 x fpyr
0.44 x length
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Kinetics of DNA Directed PNA-DNA Ligation
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Evolution of Life
Homo sapiens
Algea
Vertebrates
Earth
4.500
0.2
350
2.500
Million years