Self-replicating Molecules: An introduction

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    Self-replicating Molecules: An introduction - Presentation Transcript

    1. Self-Replication A Brief Introduction To Self-propagating Chemical Information TSRI Chemistry Journal Club 5/11/07 Brian Frezza
    2. Why Study Chemical Self-Replication
      • Evolution
        • One of the requirements for an evolvable system
      • Amplification
        • Inherent amplification useful for Chemical and Biological sensors.
      • Computation
        • Differential self-replication
      • “The Stuff of Life”
    3. A Broader Definition of Self-Replication
      • Traditionally Definition
        • Joining Reaction
      • Consider a broader non-classical definition
        • Any Chemical Information Capable of Reproducing itself.
        • What is Chemical Information?
          • Empirical Uniqueness
            • Covalent Structure
            • Supra-Molecular Interactions
            • Conformation
            • Etc…
      T •T A + B T B A B
    4. Talk Outline
      • Ligation Based Systems
        • Bio-organic
          • Hexadeoxynucleotide
          • RNA Ligase
          • Peptides
        • Synthetic
          • 3 Small Molecule Systems
      • Cleavage Based Systems
        • Ribozymes
      • Compartmentalization Based Systems
        • Autopoiesis (Self-replication of Compartments)
          • Micelles and Reverse Micelles
        • Self-replication of Location
          • Encapsulated Reagents
      • Conformation Based Systems
        • Hybridization Chain Reaction
        • Prions and Amyloids
      *unpublished work
    5. Ligation Based Self-Replication ɛ = k*/k Bg k Bg
    6. Ligation Based Self-Replication
      • Requirements:
          • Template substrate complex A • B • T forms readily
          • Template substantially accelerates the rate of it’s own production
            • Symmetry requires a palindromic template
          • Release of newly formed template occurs readily
      • Experimental Parameters
        • Epsilon (ɛ)
          • Autocatalytic Efficiency (ɛ = k */ k Bg )
          • Ratio of template-catalyzed rate over the template independent rate
            • ɛ < 1, background reaction faster then template reaction
            • ɛ approaches ∞ , no background reaction
        • Order (P)
          • Order of reaction
            • P=0.5
              • Rate-limiting dissociation
              • Parabolic amplification
              • Rate proportional to the square root of initial template concentration
            • P=1.0
              • Efficient dissociation
              • Exponential amplification
              • Rate linearly proportional to the initial template concentration
    7. Hexadeoxynucleotide Self-Replication Kiedrowski, G. Angew. Chem. Int. Ed. 1986 , 25 , 932-935.
    8. Hexadeoxynucleotide Self-Replication Kiedrowski, G. Angew. Chem. Int. Ed. 1986 , 25 , 932-935.
    9. Hexadeoxynucleotide Self-Replication P = 0.48 ɛ = ~25 Kiedrowski, G. Angew. Chem. Int. Ed. 1986 , 25 , 932-935. 0 mM Template 0.2 mM Template 0.4 mM Template 0.8 mM Template
    10. RNA Ligase Self-Replication Paul, N.; Joyce, G. F. Proc. Natl. Acad. Sci. U. S. A. 2002 , 99 , 12733-40.
    11. RNA Ligase Self-Replication Paul, N.; Joyce, G. F. Proc. Natl. Acad. Sci. U. S. A. 2002 , 99 , 12733-40.
    12. RNA Ligase Self-Replication P = ~1 ɛ = 3.0*10 8 Paul, N.; Joyce, G. F. Proc. Natl. Acad. Sci. U. S. A. 2002 , 99 , 12733-40.
    13. Peptide Self-Replication Lee, D. H.; Granja, J. R.; Martinez, J. A.; Severin, K.; Ghadri, M. R. Nature 1996 , 382 , 525-8.
    14. Peptide Self-Replication Lee, D. H.; Granja, J. R.; Martinez, J. A.; Severin, K.; Ghadri, M. R. Nature 1996 , 382 , 525-8.
    15. Peptide Self-Replication Lee, D. H.; Granja, J. R.; Martinez, J. A.; Severin, K.; Ghadri, M. R. Nature 1996 , 382 , 525-8. 0 uM Template 5 uM Template 10 uM Template 20 uM Template 40 uM Template P = ~0.5 ɛ = ~500
    16. Peptide Self-Replication
      • Modifications:
        • Shorter Template
          • Issac, R.; Chmielewski, J. J. Am. Chem. Soc. 2002 , 124 , 6808-9.
            • P=0.91
            • ɛ=1.0*10 5
        • Proline “kink” substitution
          • Li, X.; Chmielewski, J. J. Am. Chem. Soc. 2003 , 125 , 11820-1.
            • P=0.91
            • ɛ=3.2*10 4
    17. Small Molecule Self-Replication Tjivikua, T.; Ballester, P.; Rebek, J. J. Am. Chem. Soc. 1990 , 112 , 1249-1250. Wintner, E. A.; Conn, M. M.; Rebek, J. J. Am. Chem. Soc. 1994 , 116 , 8877-8884.
    18. Small Molecule Self-Replication Tjivikua, T.; Ballester, P.; Rebek, J. J. Am. Chem. Soc. 1990 , 112 , 1249-1250. A + B T A • B • T T • T Wintner, E. A.; Conn, M. M.; Rebek, J. J. Am. Chem. Soc. 1994 , 116 , 8877-8884. +
    19. Small Molecule Self-Replication Tjivikua, T.; Ballester, P.; Rebek, J. J. Am. Chem. Soc. 1990 , 112 , 1249-1250. Wintner, E. A.; Conn, M. M.; Rebek, J. J. Am. Chem. Soc. 1994 , 116 , 8877-8884. P = ~0.5 ɛ = ~22 A + B T
    20. Small Molecule Self-Replication Terfort, A.; Kiedrowski, G. Angew. Chem. Int. Ed. 1992 , 31 , 654-656.
    21. Small Molecule Self-Replication Terfort, A.; Kiedrowski, G. Angew. Chem. Int. Ed. 1992 , 31 , 654-656.
    22. Small Molecule Self-Replication Terfort, A.; Kiedrowski, G. Angew. Chem. Int. Ed. 1992 , 31 , 654-656. P = ~0.5 ɛ = ~16.4 0 Equiv. Template 0.1 Equiv. Template 0.2 Equiv. Template 0.4 Equiv. Template
    23. Small Molecule Self-Replication Pearson, R. J.; Kassianidis, E.; Slawin, A. M.; Philp, D. Org. Biomol. Chem. 2004 , 2 , 3434-41. Kassianidis, E.; Philp, D. Chem. Commun. 2006 , 4072-4. Kassianidis, E.; Philp, D. Angew. Chem. Int. Ed. 2006 , 45 , 6344-6348. Pearson, R. J.; Kassianidis, E.; Slawin, A. M.; Philp, D. Chen. Eur. J. 2006 , 12 , 6829-40.
    24. Small Molecule Self-Replication Pearson, R. J.; Kassianidis, E.; Slawin, A. M.; Philp, D. Org. Biomol. Chem. 2004 , 2 , 3434-41. A + B T Kassianidis, E.; Philp, D. Chem. Commun. 2006 , 4072-4. Kassianidis, E.; Philp, D. Angew. Chem. Int. Ed. 2006 , 45 , 6344-6348. Pearson, R. J.; Kassianidis, E.; Slawin, A. M.; Philp, D. Chen. Eur. J. 2006 , 12 , 6829-40. +
    25. Small Molecule Self-Replication Pearson, R. J.; Kassianidis, E.; Slawin, A. M.; Philp, D. Org. Biomol. Chem. 2004 , 2 , 3434-41. Kassianidis, E.; Philp, D. Chem. Commun. 2006 , 4072-4. Kassianidis, E.; Philp, D. Angew. Chem. Int. Ed. 2006 , 45 , 6344-6348. Pearson, R. J.; Kassianidis, E.; Slawin, A. M.; Philp, D. Chen. Eur. J. 2006 , 12 , 6829-40. P = ~0.1 ɛ = ~8
    26. Cleavage Based Self-Replication
      • Rather then bond making, active self-replicators are triggered by bond breaking
        • No Product Inhibition (P = 1)
      A + A A•A A
    27. Cross-Catalytic Ribozymes Levy, M.; Ellington, A. D. Proc. Natl. Acad. Sci. U. S. A. 2003 , 100 , 6416-6421.
    28. Cross-Catalytic Ribozymes Levy, M.; Ellington, A. D. Proc. Natl. Acad. Sci. U. S. A. 2003 , 100 , 6416-6421. P = 1 ɛ = 1.2*10 9
    29. Autopoiesis
      • A Compartment that catalyses the construction of more compartments.
    30. Reverse Micelles Bachmann, P. A.; Walde, P.; Luisi, P. L.; Lang, J. J. Am. Chem. Soc. 1990 , 112 , 8200-8201. Bachmann, P. A.; Walde, P.; Luisi, P. L.; Lang, J. J. Am. Chem. Soc. 1991 , 113 , 8204-8209. Bachmann, P. A.; Luisi, P. L.; Lang, J. Nature 1992 , 357 , 57-59.
    31. Reverse Micelles Bachmann, P. A.; Walde, P.; Luisi, P. L.; Lang, J. J. Am. Chem. Soc. 1990 , 112 , 8200-8201. Bachmann, P. A.; Walde, P.; Luisi, P. L.; Lang, J. J. Am. Chem. Soc. 1991 , 113 , 8204-8209. Bachmann, P. A.; Luisi, P. L.; Lang, J. Nature 1992 , 357 , 57-59.
    32. Reverse Micelles Bachmann, P. A.; Walde, P.; Luisi, P. L.; Lang, J. J. Am. Chem. Soc. 1990 , 112 , 8200-8201. Bachmann, P. A.; Walde, P.; Luisi, P. L.; Lang, J. J. Am. Chem. Soc. 1991 , 113 , 8204-8209. Bachmann, P. A.; Luisi, P. L.; Lang, J. Nature 1992 , 357 , 57-59.
    33. Locational Self-Replication
      • Free Molecule X Can Catalyze the release of molecule X from Compartment A
      X X X X X X X X X X X X + X
    34. Encapsulated Reagents Chen, J.; Korner, S.; Craig, S. L.; Lin, S.; Rudkevich, D. M.; Rebek, J., Jr. Proc. Natl. Acad. Sci. U. S. A. 2002 , 99 , 2593-6.
    35. Encapsulated Reagents Chen, J.; Korner, S.; Craig, S. L.; Lin, S.; Rudkevich, D. M.; Rebek, J., Jr. Proc. Natl. Acad. Sci. U. S. A. 2002 , 99 , 2593-6.
    36. Conformation Based Self-Replication
      • Molecule A has multiple conformations, A* is a self-replicating conformation which templates conformational change of A into A*
      A* • A* A A*
    37. Hybridization Chain Reaction (HCR) + Dirks, R. M.; Pierce, N. A. Proc. Natl. Acad. Sci. U. S. A. 2004 , 101 , 15275-8. B’ A’ B’ B A’ C’ + B’ B C A
    38. Prions and Amyloids
      • A suspected mode of action of a Prion disease is conformational self-replication that allows aggregates of the replicating conformation of a protein to accumulate in long beta sheet’s called Amyloids.
      A* A (A* • A*•) n
    39. Conclusions
      • Examples of Classic Self-Replicating by ligation have been demonstrated.
        • Improved catalytic efficiencies and reaction orders have been achieved.
        • More examples and expanded applications of self-replicators are of great interest.
      • We have just begun to explore Non-classical forms of “Self-Replication”
        • New examples, new forms, and new applications leave many exciting possibilities!

    + Brian FrezzaBrian Frezza, 10 months ago

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