Advertisement

Biomimicry as a basis for drug discovery

Chapter
Part of the Progress in Drug Research book series (PDR, volume 51)

Summary

Selected works are discussed which clearly demonstrate that mimicking various aspects of the process by which natural products evolved is becoming a powerful tool in contemporary drug discovery. Natural products are an established and rich source of drugs. The term “natural product” is often used synonymously with “secondary metabolite.” Knowledge of genetics and molecular evolution helps us understand how biosynthesis of many classes of secondary metabolites evolved. One proposed hypothesis is termed “inventive evolution.” It invokes duplication of genes, and mutation of the gene copies, among other genetic events. The modified duplicate genes, per se or in conjunction with other genetic events, may give rise to new enzymes, which, in turn, may generate new products, some of which may be selected for. Steps of the inventive evolution can be mimicked in several ways for purpose of drug discovery. For example, libraries of chemical compounds of any imaginable structure may be produced by combinatorial synthesis. Out of these libraries new active compounds can be selected. In another example, genetic system can be manipulated to produce modified natural products (“unnatural natural products”), from which new drugs can be selected. In some instances, similar natural products turn up in species that are not direct descendants of each other. This is presumably due to a horizontal gene transfer. The mechanism of this inter-species gene transfer can be mimicked in therapeutic gene delivery. Mimicking specifics or principles of chemical evolution including experimental and test-tube evolution also provides leads for new drug discovery.

Keywords

Evolution: inventive, test-tube, experimental drugs: discovery, design natural products unnatural natural products secondary metabolites gene transfer: horizontal, therapeutic algorithm: for inventive evolution, for drug discovery combinatorial synthesis 

Glossary of abbreviations

6-dEB

6-deoxyerythronolide B

PKS

polyketide synthase

FAS

fatty acid synthase

ACP

acyl carrier protein

AT

acyltransferase

KS

ketosynthase

KR

ketoreductase

DH

dehydrase

ER

enoylreductase

TE

thioesterase

EDP

electron pulse delivery

DMF

dimethylformamide

PCR

polymerase chain reaction

SELEX

systematic evolution of ligands by exponential enrichment

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    A. Burger, in: Burger’s Medicinal Chemistry, Fourth Ed., Part I. J. Wiley and Sons, New York, pp 1–54.Google Scholar
  2. 2.
    S. Omura (ed.): The Search for Bioactive Compounds from Microorganisms, Springer-Verlag, New York 1992.Google Scholar
  3. 3.
    R.P. Steiner (ed.): Folk Medicine, The Art and the Science, American Chemical Soc, Washington, D.C. 1986.Google Scholar
  4. 4.
    LJ. McGaw, A.K. Jäger and J. van Staden: Phytotherapy Res. 11, 113–117 (1997).CrossRefGoogle Scholar
  5. 5.
    M. Meckes, J. Torres, F. Calzada, J. Rivera, M. Camorlinga, H. Lemus and G. Rodriguez: Phytotherapy Res. 11, 128–131 (1997).CrossRefGoogle Scholar
  6. 6.
    G.R. Pettit, F.H. Pierson and C.L. Herald: Anticancer Drugs from Animals, Plants, and Microorganisms, J. Wiley & Sons, New York 1994.Google Scholar
  7. 7.
    M.-T. Huang, T. Osawa, C.-T. Ho and R.T. Rosen (eds.): Food Phytochemicals for Cancer Prevention I, Fruits and Vegetables, American Chemical Soc, Symposium Series 546, Washington, D.C. 1994.Google Scholar
  8. 8.
    R.V.M. Van Soest, T.M.G. Van Kempen and J.-C. Braekman (eds.): Sponges in Time and Space; Biology, Chemistry, Paleontology, A.A. Balkema Publ., Rotterdam 1994.Google Scholar
  9. 9.
    M.H.G. Munro, J.W. Blunt, RJ. Lake, M. Litaudon, C.N. Battershill and M. J. Page, in: R.V.M. Van Soest, T.M.G. Van Kempen and J.-C. Braekman (eds.): Sponges in Time and Space; Biology, Chemistry, Paleontology, A.A. Balkema Publ., Rotterdam 1994, pp. 473–484.Google Scholar
  10. 10.
    T. Hamada, T. Sugawara, S. Matsunaga and N. Fusetani, in: R.V.M. Van Soest, T.M.G. Van Kempen and J.-C. Braekman (eds.): Sponges in Time and Space; Biology, Chemistry, Paleontology, A.A. Balkema Publ., Rotterdam 1994, pp. 453–457.Google Scholar
  11. 11.
    F. J. Schmitz, in: R.V.M. Van Soest, T.M.G. Van Kempen and J.-C. Braekman (eds.): Sponges in Time and Space; Biology, Chemistry, Paleontology, A.A. Balkema Publ., Rotterdam 1994, pp. 485–496.Google Scholar
  12. 12.
    P. Juzlová, L. Martínková and V. Kren: J. Industrial Microbiol. 16, 163–170 (1996).CrossRefGoogle Scholar
  13. 13.
    J. Lederberg: The Scientist, March 17, 1997, p. 8.Google Scholar
  14. 14.
    J.W. Bennett and R. Bentley: Adv. Appl. Microbiol. 34, 1–28 (1989).CrossRefGoogle Scholar
  15. 15.
    M. Luckner: Secondary Metabolism in Microorganisms, Plants, and Animals, Third Ed., Springer-Verlag, New York 1990; a) p. 17; b) pp. 17-20; c) pp. 445-483; d) pp. 24-29.Google Scholar
  16. 16.
    K.A. Thomson, in: I.M. Chaiken and K.D. Janda (eds.): Molecular Diversity and Combinatorial Chemistry, American Chemical Soc., Washington, D.C. 1996, pp. 158–171.Google Scholar
  17. 17.
    D.A. Hopwood: Current Opinion in Biotechnology 4, 531–537 (1993).PubMedCrossRefGoogle Scholar
  18. 18.
    R.A. Maplestone, MJ. Stone and D.H. Williams: Gene 115, 151–157 (1992).PubMedCrossRefGoogle Scholar
  19. 19.
    J.W. Bennett: Can. J. Bot. 73(Suppl. 1), S917–S924 (1995).CrossRefGoogle Scholar
  20. 20.
    L.C. Vining: Gene 115, 135–140 (1992).PubMedCrossRefGoogle Scholar
  21. 21.
    L.C. Vining: Annu. Rev. Microbiol. 44, 395–427 (1990).PubMedCrossRefGoogle Scholar
  22. 22.
    L. C. Vining, in: D.J. Chadwick and J. Whelan (eds.): Secondary Metabolites: Their Function and Evolution, Ciba Foundation Symposium Series 171, J. Wiley, Chichester 1992, pp. 184–198.Google Scholar
  23. 23.
    R. Mazzarella and D. Schlessinger: Gene 205, 29–38 (1997).PubMedCrossRefGoogle Scholar
  24. 24.
    S. Ohno: Evolution by Gene Duplication, Springer, New York 1970, p. 59.Google Scholar
  25. 25.
    M.J. Stone and D.H. Williams: Molecular Microbiology 6, 29–34 (1992).PubMedCrossRefGoogle Scholar
  26. 26.
    D.J. Chadwick and J. Whelan (eds.): Secondary Metabolites: Their Function and Evolution, Ciba Foundation Symposium Series 171, J. Wiley, Chichester 1992; a) p. 271.Google Scholar
  27. 27.
    D.H. Williams and R.A. Maplestone, in: D.J. Chadwick and J. Whelan (eds.): Secondary Metabolites: Their Function and Evolution, Ciba Foundation Symposium Series 171, J. Wiley, Chichester 1992, pp. 45–63.Google Scholar
  28. 28.
    T. Cavalier-Smith, in: D.J. Chadwick and J. Whelan (eds.): Secondary Metabolites: Their Function and Evolution, Ciba Foundation Symposium Series 171, J. Wiley, Chichester 1992, pp. 64–87.Google Scholar
  29. 29.
    W.-H. Li and D. Graur: Fundamentals of Molecular Evolution, Sinauer Associates, Inc., Publ., Sunderland 1991; a) pp. 136-171; b) pp. 198-202.Google Scholar
  30. 30.
    B. Lewin: Genes V, Oxford Univ. Press, New York 1994; a) pp. 695-751; b) pp. 378-411, 413-455, 457-489.Google Scholar
  31. 31.
    A. Romberg and T.A. Baker: DNA Replication, Second Ed., W.H. Freeman and Co., New York 1992; a) pp. 836-837 and references cited therein; b) pp. 847-849.Google Scholar
  32. 32.
    J. Bailey: Genetics and Evolution, The Molecules of Inheritance, Oxford Univ. Press., New York 1995, pp. 96–97.Google Scholar
  33. 33.
    G. Bell: Selection, The Mechanism of Evolution, Chapman & Hall, Intern. Thomson Publ., New York 1997; a) p. 232; b) pp. 245-246; c) pp. 234-241; d) pp. 26-28.Google Scholar
  34. 34.
    E. Zuckerkandl: J. Mol. Evol. 44(Suppl. 1), S2–S8 (1997).PubMedCrossRefGoogle Scholar
  35. 35.
    L. Demetrius: J. Mol. Evol. 45, 370–377 (1977).CrossRefGoogle Scholar
  36. 36.
    D.A. Hopwood: Chem. Rev. 97, 2465–2497 (1997).PubMedCrossRefGoogle Scholar
  37. 37.
    D.C. Dennett: Darwin’s Dangerous Idea, Evolution and the Meaning of Life, A Touchstone Book, Simon & Schuster, Publ., New York 1996, pp. 48–60.Google Scholar
  38. 38.
    D.C. Dennett: The Sciences, May/June 1996, pp. 34-40.Google Scholar
  39. 39.
    N. Terrett: Tetrahedron News 6,1, 7 (1996).Google Scholar
  40. 40.
    S. Borman: Chemical & Engineering News, Feb. 24, 1997, pp. 43-62.Google Scholar
  41. 41.
    S.C. Stinson: Chemical & Engineering News, March 19, 1998, pp. 42, 44-46.Google Scholar
  42. 42.
    M.J. Plunkett and J.A. Ellman: Sci. Amer., April 1997, pp. 68-73.Google Scholar
  43. 43.
    S.R. Wilson and A.W. Czarnik (eds.): Combinatorial Chemistry, Synthesis and Application, J. Wiley & Sons, Inc., New York 1997.Google Scholar
  44. 44.
    I.M. Chaiken and K.D. Janda (eds.): Molecular Diversity and Combinatorial Chemistry, American Chemical Society, Washington, D.C. 1998.Google Scholar
  45. 45.
    Chem. Rev. 2 (1997), Thematic issue on Combinatorial Chemistry.Google Scholar
  46. 46.
    K.S. Lam, M. Lebl and V. Krchnák: Chem. Rev. 97, 411–448 (1997).PubMedCrossRefGoogle Scholar
  47. 47.
    S.R. Wilson, in: S.R. Wilson and A.W. Czarnik (eds.): Combinatorial Chemistry, Synthesis and Application, J. Wiley & Sons, Inc., New York 1997, pp. 1–23.Google Scholar
  48. 48.
    D.J. Gravert and K.D. Janda: Chem. Rev. 97, 489–509 (1997).PubMedCrossRefGoogle Scholar
  49. 49.
    E.A. Wintner and J. Rebek, Jr., in: S.R. Wilson and A.W. Czarnik (eds.): Combinatorial Chemistry, Synthesis and Application, J. Wiley & Sons, Inc., New York 1997, pp. 95–117.Google Scholar
  50. 50.
    A. Nefzi, J.M. Ostresh and R.A. Houghten: Chem. Rev. 97, 449–472 (1997).PubMedCrossRefGoogle Scholar
  51. 51.
    G.P. Smith and V.A. Petrenko: Chem. Rev. 97, 391–410 (1997).PubMedCrossRefGoogle Scholar
  52. 52.
    S.E. Osborne and A.D. Ellington: Chem. Rev. 97, 349–370 (1997).PubMedCrossRefGoogle Scholar
  53. 53.
    M.C. Pirrung: Chem. Rev. 97, 473–488 (1977).CrossRefGoogle Scholar
  54. 54.
    S.H. DeWitt and A.W. Czarnik, in: S.R. Wilson and A.W. Czarnik (eds.): Combinatorial Chemistry, Synthesis and Application, J. Wiley & Sons, Inc., New York 1997, pp. 25–38.Google Scholar
  55. 55.
    M.R. Spiegel: Theory and Problems of Probability and Statistics, Schaum’s Outline Series, McGraw-Hill, Inc., New York 1992, pp. 9–11, 23-27.Google Scholar
  56. 56.
    M. Sternstein: Statistics, Barron’s Educational Series, Inc., Hauppauge, N.Y. 1996, pp. 43–49.Google Scholar
  57. 57.
    J.C. Roberts, B.E. Thomas, Y. Shen, A. Melikian-Badalian, P.J. Kowalczyk and P.V. Pallai, in: I.M. Chaiken and K.D. Janda (eds.): Molecular Diversity and Combinatorial Chemistry, American Chemical Society, Washington, D.C. 1998, pp. 10–15.Google Scholar
  58. 58.
    X.-Y. Xiao and M.P. Nova, in: S.R. Wilson and A.W. Czarnik (eds.): Combinatorial Chemistry, Synthesis and Application, J. Wiley & Sons, Inc., New York 1997, pp. 135–152.Google Scholar
  59. 59.
    D.G.I. Kingston, B.-N. Zhou, M.S. Abdel-Kader, J.M. Berger and S.-W Yang: Biodiversity Conservation and Drug Discovery. Exploration in Suriname’s Tropical Rainforest, 215th Natl. Meeting of Amer. Chem. Soc., Dallas, Texas, March 29–April 2, 1998, Abstract ORG-132.Google Scholar
  60. 60.
    M. Qabar, J. Urban, C. Sia, M. Klein and M. Kahn,in: I.M. Chaiken and K.D. Janda (eds.): Molecular Diversity and Combinatorial Chemistry, American Chemical Society, Washington, D.C. 1998, pp. 2–9.Google Scholar
  61. 61.
    M.A. Wuonola and D.G. Powers, in: I.M. Chaiken and K.D. Janda (eds.): Molecular Diversity and Combinatorial Chemistry, American Chemical Society, Washington, D.C. 1998, pp. 284–297.Google Scholar
  62. 62.
    D.A. Hopwood and C. Khosla, in: DJ. Chadwick and J. Whelan (eds.): Secondary Metabolites: Their Function and Evolution, Ciba Foundation Symposium Series 171, J. Wiley, Chichester 1992, pp. 88–112.Google Scholar
  63. 63.
    R. McDaniel, S. Ebert-Khosla, D.A. Hopwood and C. Khosla: Science 262, 1546–1550 (1993).PubMedCrossRefGoogle Scholar
  64. 64.
    C.J. Tsoi and C. Khosla: Chemistry & Biology 2, 355–362 (1995).CrossRefGoogle Scholar
  65. 65.
    R. Pieper, C. Kao, C. Khosla, G. Luo and D.E. Cane: Chem. Rev. 25, 297–302 (1996).CrossRefGoogle Scholar
  66. 66.
    J.R. Jacobsen, C.R. Hutchinson, D.E. Cane and C. Khosla: Science 277, 367–369 (1997).PubMedCrossRefGoogle Scholar
  67. 67.
    C.R. Hutchinson, H. Decker, P. Guilfoile, B. Shen, R. Summers, E. Wendt-Pienkowski and B. Wessel, in: R.J. Petroski and S.P. McCormick (eds.): Secondary-Metabolite Biosynthesis and Metabolism, Plenum Press, New York 1992, pp. 3–10.CrossRefGoogle Scholar
  68. 68.
    L. Katz and S. Donadio: Annu. Rev. Microbiol. 47, 875–912 (1993).PubMedCrossRefGoogle Scholar
  69. 69.
    S. Donadio, M.J. Staver, J.B. McAlpine, S.J. Swanson and L. Katz: Science 252, 675–679 (1991).PubMedCrossRefGoogle Scholar
  70. 70.
    L. Katz and C.R. Hutchinson: Annu. Reports in Medicinal Chem. 27, 129–138 (1992).CrossRefGoogle Scholar
  71. 71.
    L. Katz: Chem. Rev. 97, 2557–2575 (1997).PubMedCrossRefGoogle Scholar
  72. 72.
    C. Khosla: Chem. Rev. 97, 2577–2590 (1977).CrossRefGoogle Scholar
  73. 73.
    CM. Kao, M. McPherson, R.N. McDaniel, H. Fu, D.E. Cane and C. Khosla: J. Amer. Chem. Soc. 120, 2478–3479 (1998).CrossRefGoogle Scholar
  74. 74.
    A.EA. Mardsen, B. Wilkinson, J. Cortes, N.J. Dunster, J. Staunton and P.F. Leadlay: Science 279, 199–202 (1998).CrossRefGoogle Scholar
  75. 75.
    R.L. Rawls: Chemical & Engineering News, March 9, 1998, pp. 29-32.Google Scholar
  76. 76.
    YL. Khmelnitsky, P.C. Michels, J.S. Dodick and D.S. Clark, in: I.M. Chaiken and K.D. Janda (eds.): Molecular Diversity and Combinatorial Chemistry, American Chemical Society, Washington, D.C. 1998, pp. 144–157.Google Scholar
  77. 77.
    S.K. Wrigley and M.I. Chicarelli-Robinson: Annu. Reports in Medicinal Chem. 32, 285–294 (1997).CrossRefGoogle Scholar
  78. 78.
    T. Friedmann, in: Special Report; Making Gene Therapy Work, Sci. Amer., June 1997, pp. 96-101.Google Scholar
  79. 79.
    P.L. Feigner, in: Special Report, Making Gene Therapy Work, Sci. Amer., June 1997, pp. 102-110.Google Scholar
  80. 80.
    R.M. Blaese, in: Special Report, Making Gene Therapy Work, Sci. Amer., June 1997, pp. 111-115.Google Scholar
  81. 81.
    D.Y. Ho and R.M. Sapolsky, in: Special Report, Making Gene Therapy Work, Sci. Amer., June 1997, pp. 116-120.Google Scholar
  82. 82.
    S. Mirsky and J. Rennie, in: Special Report, Making Gene Therapy Work, Sci. Amer., June 1997, pp. 122-123.Google Scholar
  83. 83.
    P.L. Feigner, M.J. Heller, P. Lehn, J.P. Behr and F.C. Szoka (eds.): Artificial Self-Assembling Systems for Gene Delivery, American Chemical Society, Washington, D.C. 1996.Google Scholar
  84. 84.
    X. Zhao, in: P.L. Feigner, MJ. Heller, P. Lehn, J.P. Behr and F.C. Szoka (eds.): Artificial Self-Assembling Systems for Gene Delivery, American Chemical Society, Washington, D.C. 1996, pp. 63–71.Google Scholar
  85. 85.
    J.C. Perales, M. Molas and R.W. Hanson, in: P.L. Feigner, M.J. Heller, P. Lehn, J.P. Behr and F.C. Szoka (eds.): Artificial Self-Assembling Systems for Gene Delivery American Chemical Society, Washington, D.C. 1996, pp. 105–119.Google Scholar
  86. 86.
    A. Kichler, W. Zauner, C. Morrison and E. Wagner, in: P.L. Feigner, MJ. Heller, P. Lehn, J.P. Behr and F.C. Szoka (eds.): Artificial Self-Assembling Systems for Gene Delivery, American Chemical Society, Washington, D.C. 1996, pp. 120–128.Google Scholar
  87. 87.
    B.A. Demeneix and J.P. Behr, in: P.L. Feigner, M.J. Heller, P. Lehn, J.P. Behr and F.C. Szoka (eds.): Artificial Self-Assembling Systems for Gene Delivery, American Chemical Society, Washington, D.C. 1996, pp. 146–151.Google Scholar
  88. 88.
    S.B. Levy: Sci. Amer., March 1998, pp. 46-53.Google Scholar
  89. 89.
    D. Ferber: Science 280, 27 (1998).PubMedCrossRefGoogle Scholar
  90. 90.
    R.V. Miller: Sci. Amer., January 1998, pp. 66-71.Google Scholar
  91. 91.
    F. Flam: Science 265, 1032–1033 (1994).PubMedCrossRefGoogle Scholar
  92. 92.
    F.H. Arnold: Acc. Chem. Res. 31, 125–131 (1998).CrossRefGoogle Scholar
  93. 93.
    A.A. Beaudry and G.F. Joyce: Science 257, 635–641 (1992).PubMedCrossRefGoogle Scholar
  94. 94.
    N. Lehman and G. F. Joyce, “Evolution in Vitro: Analysis of a Lineage of Ribozymes”, Current Biology, 3, 723–724 (1993).CrossRefGoogle Scholar
  95. 95.
    N. Lehman and G. F. Joyce: Nature 361, 182–185 (1993).PubMedCrossRefGoogle Scholar
  96. 96.
    M.C. Wright and G.F. Joyce: Science 276, 614–617 (1997).PubMedCrossRefGoogle Scholar
  97. 97.
    A.D. Ellington, M.P. Robertson and J. Bull: Science 276, 546–547 (1997).PubMedCrossRefGoogle Scholar
  98. 98.
    Chemical & Engineering News, Dec. 22, 1997, p. 37.Google Scholar
  99. 99.
    G. Cziko: Without Miracles, Universal Selection Theory and the Second Darwinian Revolution, The MIT Press, Cambridge, MA 1995, pp. 274–277.Google Scholar
  100. 100.
    M.R. Rose, T.J. Nusbaum and A.K. Chippindale, in: M.R. Rose and G.V. Lauder (eds.): Adaptation, Academic Press, New York 1996, pp. 221–241.Google Scholar
  101. 101.
    J.W. Szostak: Chem. Rev. 97, 347–348 (1997).PubMedCrossRefGoogle Scholar
  102. 102.
    R.R. Breaker: Chem. Rev. 97, 371–390 (1997).PubMedCrossRefGoogle Scholar
  103. 103.
    N. Usman and J.A. McSwiggen: Annu. Reports in Medicinal Chem. 30, 285–294 (1995).CrossRefGoogle Scholar
  104. 104.
    V.M. Kolb: Progress in Drug Research 48, 195–232 (1997).PubMedGoogle Scholar

Copyright information

© Springer Basel AG 1998

Authors and Affiliations

  1. 1.Department of ChemistryUniversity of Wisconsin-ParksideKenoshaUSA

Personalised recommendations