Biologically Active Peptides from Microorganisms and Fungi

  • Theodor Wieland
  • Miklos Bodanszky


In Chap. 1 (p. 14) a few naturally occurring peptides were presented as substances which quite early aroused the attention of chemists at a time when peptide chemistry still led a hidden existence. With the recognition that several hormones consist of amino acids (see Chap. 7), and with the discovery of microbial products which exhibit antibiotic or toxic properties and were also built from amino acids, interest in such materials greatly increased. In the following years amino acids were identified as building blocks of biologically active substances which had been recognized and isolated many years before pharmacologists and physicians knew about their peptide-like nature.


Active Peptide Cyclic Peptide Ergot Alkaloid Microcystis Aeruginosa Peptide Antibiotic 
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  1. 1.
    A. Hofmann, H. Ott, R. Griot, P.A. Stadler, A.J. Frey, Synthese von Ergotamin, Helv. Chim. Acta 46: 2306–2336 (1963).CrossRefGoogle Scholar
  2. 2.
    R.G. Griot, A.J. Frey, The formation of cyclols from N-hydroxyacyl lactames, Tetrahedron 19:1661–1673 (1963).CrossRefGoogle Scholar
  3. 3.
    M.M. Shemyakin, V.K. Antonov, A.M. Shkrob, Activation of the amide group by acylation, Peptides, Proc. 6th Europ. Pept. Symp., Athens 1963, 319-328.Google Scholar
  4. 4.
    G. Lucente, A. Romeo, Synthesis of cyclols from small peptides via amide-amide reaction, Chem. Commun. 1605-1607 (1971).Google Scholar
  5. 5.
    M. Rothe, W. Schindler, R. Pudill, U. Kostrzewa, R. Theyson, R. Steinberger, Zum Problem der Cyclotripeptidsynthese, Peptides, Proc. 11th Europ.-Pept. Symp. Wien 1971, 388-399.Google Scholar
  6. 6.
    M. Rothe, K.-L. Roser, Conformational flexibility of cyclic tripeptides, Abstr. 20th Europ. Pept. Symp. Tübingen 1988, p. 36.Google Scholar
  7. 7.
    Th. Wieland, H. Mohr, Diacylamide als energiereiche Verbindungen. Diglycylimid. Liebigs Ann. Chem. 599: 222–232 (1956); Th. Wieland, H. Urbach, Weitere Di-Aminoacylimide und ihre intramolekulare Umlagerung. Liebigs Ann. Chem. 613: 84-95 (1958).CrossRefGoogle Scholar
  8. 8.
    M. Brenner, The aminoacyl insertion in: Ciba Foundation Sympos. on Amino acids and peptides with antimetabolic activity. G.E.W. Wolstenholme and CM. O’Connor eds. Churchill, London 1958 pp 157–170.Google Scholar
  9. 9.
    G. Zanotti, F. Pinnen, G. Lucente, S. Cerrini, W. Fedeli, F. Mazza. Peptide thiacyclols. Synthesis and structural studies, J. Chem. Soc. Perkin Trans. 1 1984, 1153–1157.CrossRefGoogle Scholar
  10. 10.
    H.T. Clarke, J.R. Johnson, R. Robinson, The Chemistry of Penicillin Princeton University Press, Princeton, N.J., 1949.Google Scholar
  11. 11.
    H.R.V. Arnstein, D. Morris, The structure of a peptide containing α-amino-adipic acid in the mycelium of Penicillium chyrsogenum. Biochem. J. 76: 357–361 (1960).PubMedGoogle Scholar
  12. 12.
    D.J. Hook, R.P. Elander, R.B. Morin, Recent developments with cell free extracts on the enzymic biosynthesis of penicillins and cephalosporins in “Peptide-antibiotics”. Biosynthesis and Function, H. Kleinkauf, H. von Döhren eds. de Gruyter, Berlin 1982, pp 84–100.Google Scholar
  13. 13.
    E.P. Abraham, The cepholosporin C group. Quart. Rev. 21: 231–248 (1967).CrossRefGoogle Scholar
  14. 14.
    R.B. Woodward, K. Heusler, J. Gosteli, P. Naegeli, W. Oppolzer, R. Ramage, S. Ranaganathan, H. Vorbrüggen, The total synthesis of cephalosporin G, J. Amer. Chem. Soc. 88: 852–853 (1966).CrossRefGoogle Scholar
  15. 15.
    H. Brockmann, G. Schmidt-Kastner, Valinomycin I. XXVII. Mitt. über Antibiotica aus Actinomyceten, Chem. Ber. 88: 57–61 (1955).CrossRefGoogle Scholar
  16. 16.
    C. Moore, B.C. Pressman, Mechanism of action of valinomycin on mitochondria, Biochem. Biophys. Res. Com. 15: 562–567 (1964).CrossRefGoogle Scholar
  17. 17.
    Yu. A. Ovchinnikov, V.T. Ivanov, A.M. Shkorb, in Membrane-active complexones, BBA Library, Vol. 12 Elsevier, Amsterdam 1974.Google Scholar
  18. 18.
    K. Neupert-Laves, M. Dobler, The crystal structure of a K+-complex of valinomycin, Helv. Chim. Acta 58: 432–442 (1975).PubMedCrossRefGoogle Scholar
  19. 19.
    M.M. Shemyakin, N.A. Aldanova, E.I. Vinogradova, M.Y. Feigina, The structure and total synthesis of valinomycin, Tetrahedron Lett. 1963:1921-1925. See also V.T. Ivanov, Yu.A. Ovchinnikov, A.A. Kiryushkin, M.M. Shemyakin, Synthetic and natural desipeptides, Peptides Proc. 6th Eur. Pep. Symp. (L. Zervas ed) Pergamon 1963, pp 337-350.Google Scholar
  20. 20.
    D. Baron, L.G. Pease, E.R. Blout, Cation binding of a cyclic dodecapeptide cyclo-(l-Val-Gly-Gly-l-Pro)3 in an aprotic medium. J. Amer. Chem. Soc. 99: 8299–8306 (1977).CrossRefGoogle Scholar
  21. 21.
    J. Dominguez, J.D. Demitz, H.H. Gerlach, V. Prelog, Stoffwechselprodukte von Aktinomy-ceten. Über die Konstitution von Nonactin. Helv. Chim. Acta 45:129–138 (1962).CrossRefGoogle Scholar
  22. 22.
    CJ. Pedersen, H.K. Frensdorff, Makrozyklische Polyäther und ihre Komplexe. Angew. Chem. 84: 16–26 (1972).CrossRefGoogle Scholar
  23. 23.
    J.-M. Lehn, Supramolekulare Chemie—Moleküle, Übermoleküle und molekulare Funktionseinheiten (Nobel-Vortrag) Angew. Chem. 100: 92–116 (1988).Google Scholar
  24. 24.
    R. Consden, A.H. Gordon, AJ.P. Martin, R.L.M. Synge, Gramicidin S: the sequence of the amino acid residues. Biochem. J. XLIII-XLIV (1946).Google Scholar
  25. 25.
    R. Schwyzer, P. Sieber, Die Synthese von Gramicidin S, Helv. Chim. Acta 40: 624–639 (1957).CrossRefGoogle Scholar
  26. 26.
    Th. Wieland, K.W. Ohly, Über Peptidsynthesen XVI., Peptidcyclisierungen mit Car-bodiimiden, Liebigs Ann. Chem. 605: 179–182 (1957).CrossRefGoogle Scholar
  27. 27.
    J.C. Sheehan, M. Goodman, W.L. Richardson, The product derived from the cyclization of triglycine azide. J. Amer. Chem. Soc. 77: 6391 (1955).CrossRefGoogle Scholar
  28. 28.
    R.O. Studer, Synthesis and structure of fungisporin, Experimentia 25: 899 (1969).Google Scholar
  29. 29.
    R. Schwyzer, P. Sieber, Verdopplungsreaktionen beim Ringschluβ von Peptiden, I. Synthese von Gramicidin S und von bis-homo-Gramicidin S aus den Pentapeptid-Einheiten. Helv. Chim. Acta 41: 2186–2189 (1958).CrossRefGoogle Scholar
  30. 30.
    H.G. Zachau, G. Acs, F. Lipmann, Isolation of adenosine amino acid esters from a ribonuclease digest of soluble, liver ribonucleic acid. Proc. Natl. Acad. Sci. USA 44: 885–889 (1958).PubMedCrossRefGoogle Scholar
  31. 31.
    See e.g. Th. Wieland, Sulfur in biomimetic peptide syntheses, In Roots of Biochemistry, Fritz Lipmann-Meeting, Berlin 1987. H. Kleinkauf, H.v. Döhren, L. Jaenicke eds., de Gruyter, Berlin 1988, pp 213-223. In this book one finds i.a. reviews on history of biological peptide syntheses.Google Scholar
  32. 32.
    W. Gevers, H. Kleinkauf, F. Lipmann, Peptidyl transfers in gramicidin S biosynthesis from enzyme bound thiolester intermediates. Proc. Natl. Acad. Sci. USA 63:1334–1342 (1969).CrossRefGoogle Scholar
  33. 33.
    R. Sarges, B. Witkop, Gramicidin VIII. The structure of valine-and isoleucine-gramicidin C, Biochemistry 4: 2491–2494 (1965).CrossRefGoogle Scholar
  34. 34.
    C.E. Meyer, F. Reusser, A polypeptide antibacterial agent isolated from Trichoderma viride. Experientia 23: 85–86 (1967).PubMedCrossRefGoogle Scholar
  35. 35.
    G. Boheim, H.A. Kolb, Analysis of the multi-pore system of alamethicin in a lipid membrane. I. Voltage-jump current-relaxation measurements, J. Membrane Biol. 38: 99–150 (1978).CrossRefGoogle Scholar
  36. 36.
    J.F. Borel, C. Feurer, H.V. Gubler, H. Stähelin. Biological effects of cyclosporin A: a new antilymphocytic agent. Agnets Actions 6: 468–475 (1976).CrossRefGoogle Scholar
  37. 37.
    A. Rüegger, M. Kuhn, H. Lichti, H.-R. Loesli, R. Huguenin, Ch. Quiquerez, A.v. Wartburg, Cyclosporin A, ein immunsuppresiv wirksamer Peptidmetabolit aus Trichoderma polysporum (Link ex Pers.) Rifai, Helv. Chim. Acta 59: 1075–1092 (1976).PubMedCrossRefGoogle Scholar
  38. 38.
    R.M. Wenger, Synthesis of cyclosporine. Total synthesis of “cyclosporin A” and “cyclosporin H” two fungal metabolites isolated from the species Tolypocladium inflatum Gams, Helv. Chim. Acta 67: 502–525 (1984).CrossRefGoogle Scholar
  39. 39.
    H. Kobel, R. Traber, Directed biosynthesis of cyclosporins, Eur. J. Appl. Microbiol. Biotechnol 1. 14: 237–240 (1982).CrossRefGoogle Scholar
  40. 40.
    A. Billich, R. Zocher, Enzymatic synthesis of cyclosporin A, J. Biol. Chem. 262: 17258–17259 (1987).PubMedGoogle Scholar
  41. 41.
    Th. Wieland, Peptides of poisonous Amanita mushrooms. A. Rich ed., Springer Verlag, Berlin Heidelberg New York 1986.Google Scholar
  42. 42.
    Th. Wieland, G. Lüben, H.C.J. Ottenheym, J. Faesel, J.X. de Vries, W. Konz, A. Prox, J. Schmid, The discovery, isolation, elucidation of structure and synthesis of antamanide, Angew. Chem. Int. Ed. Engl. 7: 204–208 (1968).PubMedCrossRefGoogle Scholar
  43. 43.
    Th. Wieland, M. Nassal, W. Kramer, G. Fricker, U. Bickel, G. Kurz, Identity of hepatic membrane transport systems for bile salts, phalloidin, and antamanide by photoaffinity labeling, Proc. Natl. Acad. Sci. USA 81: 5232–5236 (1984).PubMedCrossRefGoogle Scholar
  44. 44.
    For details see e.g. W. Burgermeister, R. Winkler-Oswatitsch, Topics in current Chemistry, Complex formation of monovalent cations with bifunctional ligands. F.L. Boschke ed., Springer-Verlag Berlin Heidelberg New York 1977, pp. 91–196.Google Scholar
  45. 45.
    I.L. Karle, J. Karle, Th. Wieland, W. Burgermeister, H. Faulstich, B. Witkop, Conformation of the Li-antamanide complex and Na [Phe4, Val6] antamanide complex in the crystalline state. Proc. Natl. Acad. Sci. USA 70:1836–1840 (1973).PubMedCrossRefGoogle Scholar
  46. 46.
    I.L. Karle, Th. Wieland, D. Schermer, H.C.J. Ottenheym, Conformation of uncomplexed, natural antamanide crystallized from CH3CN/H2O. Proc. Natl. Acad. Sci. USA 76:1532–1536 (1979).PubMedCrossRefGoogle Scholar
  47. 47a.
    W. Burgermeister, Th. Wieland, R. Winkler-Oswatitsch. Antamanide. Relaxation study of conformational equilibria, Eur. J. Biochem. 44: 311–316 (1974).PubMedCrossRefGoogle Scholar
  48. 47b.
    H. Kessler, J.W. Bats, J. Lautz, A. Müller, Conformation of antamanide, Liebigs Ann. Chem. 1989:913-928.Google Scholar
  49. 48.
    H.P. Kaufmann, A. Tobschirbel, Über ein Oligopeptid aus Leinsamen, Chem. Ber. 92: 2805–2809 (1959).CrossRefGoogle Scholar
  50. 49.
    H. Kessler, M. Gehrke, A. Haupt, M. Klein, A. Müller, K. Wagner, Common structural features of cytoprotection activities of somatostatin, antamanide and related peptides, Klin. Wochenschr. 64: 74–78 (1986).PubMedGoogle Scholar
  51. 50.
    H. Faulstich, A. Buku, H. Bodenmüller, Th. Wieland, Virotoxins: actin-binding cyclic peptides of Amanita virosa mushrooms, Biochemistry 19: 334–343 (1980).CrossRefGoogle Scholar
  52. 51.
    E. Munekata, H. Faulstich, Th. Wieland, Totalsynthese des Phalloins und Leu3-phalloins, Liebigs Ann. Chem. 1977: 1758-1765.Google Scholar
  53. 52.
    A recent review: H. Faulstich, S. Zobeley, G. Rinnerthaler, J.V. Small, Fluorescent phallotoxins as probes for filamentous actin, J. Muscle Res. Cell Motility 9: 370–383 (1988).CrossRefGoogle Scholar
  54. 53.
    A. Baku, Th. Wieland, H. Bodenmüller, H. Faulstich, Amaninamide, a new toxin of Amanita virosa mushrooms, Experientia 36:-36–34 (1980).CrossRefGoogle Scholar
  55. 54.
    H. Faulstich, The amatoxins, Progr. Mol. Subcell. Biol. 7: 88–134 (1980).CrossRefGoogle Scholar
  56. 55.
    Th. Wieland, U. Gebert, Strukturen der Amanitine, Liebigs Ann. Chem. 700:157–173 (1966).CrossRefGoogle Scholar
  57. 56.
    E.C. Kostansek, W.N. Lipscomb, R.R. Yocum, W.E. Thiessen, The crystal structure of the mushroom toxin β-amanitin. J. Amer. Chem. Soc. 99:1273–1274 (1977).CrossRefGoogle Scholar
  58. 57.
    C.T. Bishop, E.F.L.J. Anet, P.R. Gorham, Isolation and identification of the fast-death factor in Microcystis aeruginosa NRC-1. Can. J. Biochem. Physiol. 37: 453-(1959).PubMedCrossRefGoogle Scholar
  59. 58.
    D.P. Botes, A.A. Tuimman, P.L. Wessels, C.C. Viljoen, H. Kruger, D.H. Williams, S. Santikarn, R.J. Smith, SJ. Hammond, The structure of cyanoginosin-LA, a cyclic heptapeptide toxin from the cyanobacterium Microcystis aeruginosa. J. Chem. Soc. Perkin Trans. 1984: 2311-2318.Google Scholar
  60. 59.
    In order to unify the nomenclature 14 laboratories in a letter to the editor have suggested the name “microcystin” with the two letter suffic XY: Naming of cyclic heptapeptide toxins of cyanobacteria (blue-green algae), Toxicon 26: 971-973 (1988).Google Scholar
  61. 60.
    M.T.C. Runnegar, I.R. Falconer, Effect of toxin from the cyanobacterium Microcystis aeruginosa on ultrastructure morphology and actin polymerization in isolated hepatocytes Toxicon 24: 109–115 (1986).Google Scholar
  62. 61.
    K. Fukase, M. Kitazawa, A. Sano, K. Shimbo, H. Fujita, S. Horimoto, T. Wakamiya, and T. Shiba, Total synthesis of peptide antibiotic Nisin, Tetrahedron Lett. 795-798 (1988).Google Scholar
  63. 62.
    N. Schnell, K.-D. Entian, U. Schneider, F. Götz, H. Zähner, R. Kellner, G. Jung, Prepeptide sequenz of epidermin, a ribosomally synthesized antibiotic with four sulfide-rings, Nature 333:276–278(1988).PubMedCrossRefGoogle Scholar
  64. 63.
    H. Lackner, Die Raumstruktur der Actinomycine, Angew. Chem. 87:400–411 (1975).CrossRefGoogle Scholar
  65. 64.
    See Antibiotics III (J.W. Corwran and F.H. Hahn, eds.) Springer, Berlin Heidelberg. New York 1975.Google Scholar
  66. 65.
    For an overview see E.W. Warnhoff, Peptide alkaloids in Progress in the Chemistry of Organic Natural Products, W. Herz, H. Griesebach, A.I. Scott eds. Springer, Vienna New York Vol. 28, 162–203 (1970).Google Scholar
  67. 66.
    U. Schmidt, Natürliche Cyclopeptide und Cyclopeptolide, Nachr. aus Chemie und Technik 57:1034–1042 (1989).Google Scholar

Copyright information

© Spinger-Verlag Berlin Heidelberg 1991

Authors and Affiliations

  • Theodor Wieland
    • 1
  • Miklos Bodanszky
    • 2
  1. 1.Max-Planck-Institut für Medizinische ForschungHeidelbergGermany
  2. 2.PrincetonUSA

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