Effects of Structure of Active Compounds on Biological Activity and Specificity

  • Daniel H. Rich
Part of the NATO Advanced Study Institutes Series book series (NSSA, volume 10)


It is probable that the chemical basis of resistance and specificity will be found in part from studies of the interactions of toxins with plants susceptible and resistant to those toxins. The Phytotoxins with the most selective toxicity are the host-specific toxins; these are much more active in altering the metabolism of host plants susceptible to the toxin-producing micro-organism. Many host-specific toxins are unusually potent causing biological effects at concentrations less than 10-10 g/ml. The specificity and potency of these toxins suggest that they efficiently inhibit important biochemical processes in susceptible plants. Resistant plants either lack these pathways or possess mechanisms that protect against the action of the toxin. Elucidation of these resistance mechanisms will greatly increase our knowledge of specificity. Unfortunately the instability and chemical complexity of certain host-specific toxins have complicated mechanism of action studies because of uncertainties about chemical purity and concentration and by making structure determinations very difficult.


Dihydrofolate Reductase Selective Toxicity Compound XVII Full Biological Activity Cyclic Tetrapeptide 
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  1. 1.
    ARIENS, E.J. (1964). Molecular Pharmacology, Vol. 1, 136–286. Academic Press, New York and London.Google Scholar
  2. 2.
    BAKER, B.R. (1967). Design of active-site-directed irreversible enzyme inhibitors. John Wiley and Sons, New York, 325 pp.Google Scholar
  3. 3.
    Buchanan, J.M. (1958). Mechanism of action of azaserine. In: Amino acids and peptides with antimetabolic activity. (Wostenholme, C.E.W. and O’connor, C.M., Eds.). CIBA Foundation Symposium. Academic Press, New York and London.Google Scholar
  4. 4.
    DALE, J., and TITLESTAD, K. (1969). Cyclic oligopeptides of sarcosine. J. chem. Soc., Chem. Communs, 656.Google Scholar
  5. 5.
    DALE, J., and TITLESTAD, K. (1970). A common conformation for five cyclic tetrapeptides. J. chem. Soc., Chem. Communs, 1403.Google Scholar
  6. 6.
    DARDENNE, G., CASIMIR, J., MARLIER, M., and LARSEN, P.O. (1974). Acide 2(R)-Amino-3-Butenoique (Vinylglycine) dans les carpophores de Rhodophyllus nidorosus. Phytochemistry, 13, 1897 – 1900.CrossRefGoogle Scholar
  7. 7.
    GROSS, E. and MORELL, J.L. (1971). The structure of nisin. J. Am. chem. Soc., 93, 4634 – 4635.PubMedCrossRefGoogle Scholar
  8. 8.
    HANSCH, C. and CLAYTON, J.M. (1973). Lipophilic character and biological activity of drugs II: The parabolic case. J. pharm. Sci., 62, 1–21.PubMedCrossRefGoogle Scholar
  9. 9.
    HANSCH, C. and DUNN, W.J. (1972). Linear relationships between lipophilic character and biological activity of drugs. J. pharm. Sci., 61, 1 – 19.PubMedCrossRefGoogle Scholar
  10. 10.
    HITCHINGS, G.H. and BURCHALL, J.J. (1965). Inhibitions of folate biosynthesis and function as a basis for chemotherapy. Adv. Enzymol., 27, 417 – 468.PubMedGoogle Scholar
  11. 11.
    KONCEWICZ, M., MATHIAPARANAM, P., UCHYTIL, T.F., SPARAPANO, L., TAM, J., RICH, D.H. and DURBIN, R.D. (1973). The sequence and optical configuration of the amino acids in tentoxin. Biochem. biophys. Res. Commun., 53, 653 – 658.PubMedCrossRefGoogle Scholar
  12. 12.
    LEE, B. (1971). Conformation of penicillin as a transitionstate analog of the substrate of peptidoglycon transpeptidase. J. molec. Biol., 61, 463 – 469.PubMedCrossRefGoogle Scholar
  13. 13.
    LIENHARD, G.E. (1972). Transition-state analogs as enzyme inhibitors. A. Rep. Med. Chem., 7, 249 – 258.Google Scholar
  14. 14.
    MEYER, W.L., KUYPER, L.F., LEWIS, R.B., TEMPLETON, G.E. and WOODHEAD, S.H. (1974). The amino acid sequence and configuration of tentoxin. Biochem. biophys. Res. Commun., 56, 234 – 240.PubMedCrossRefGoogle Scholar
  15. 15.
    MEYER, W.L., KUYPER, L.F., PHELPS, D.W. and CORDES, A.W. (1975). Use of 1H Nmr spectroscopy for sequence and configurat-ional analysis of cyclic peptides. The structure of tentoxin. J. Am. chem. Soc., 97, 3802 – 3809.CrossRefGoogle Scholar
  16. 16.
    OKUNO, T., ISHITA, T., SAWAI, K., and MATSUMOTO, T. (1974). Alternariolide, host-specific toxin produced by Alternaria mali Roberts. Chem. Lett., 635 – 638.Google Scholar
  17. 17.
    RANDO, R.R. (1974). Chemistry and enzymology of kcat inhibitors. Science, N.Y., 185, 320 – 324.CrossRefGoogle Scholar
  18. 18.
    RANDO, R.R. (1975). Mechanisms of action of naturally occurring irreversible enzyme inhibitors. Acc. chem. Res., 8, 281 – 288.CrossRefGoogle Scholar
  19. 19.
    RICH, D.H. and MATHIAPARANAM, P. (1974). The synthesis of the cyclic tetrapeptide, tentoxin. Effect of an N-methyl de-hydrophenylalanyl residue on conformation of linear peptides. Tetrahedron Lett., 46, 4037 – 4040.CrossRefGoogle Scholar
  20. 20.
    RICH, D.H., TAM, J., MATHIAPARANAM, P., GRANT, J.A., and MABUNI, C., (1974). General synthesis of didehydro amino acids and peptides. J. chem. Soc., Chem. Communs, 897 – 898.Google Scholar
  21. 21.
    RICH, D.H., Tam, J., Mathiaparanam, P., and Grant, J.A. (1975). Selective N-methylation of dehydro amino acids and peptides. Synthesis, 402 – 403.Google Scholar
  22. 22.
    RICH, D.H., MATHIAPARANAM, P., GRANT, J.A., and BHATNAGAR, P. (1975). Synthesis of cyclic tetrapeptides related to tentoxin. In: PeptidesChemistry, Structure and Biology. Walter, R. and Meienhofer, J., Eds.). Proc. 4th Am. Peptide Symp., Ann. Arbor Science Publishers, Inc. (In press).Google Scholar
  23. 23.
    SINGER, S.J. (1967). Covalent labeling of active sites. Adv. Protein Chem., 22, 1 – 54.PubMedCrossRefGoogle Scholar
  24. 24.
    SPEK, A.L., PEERDEMAN, A.F., VAN WIDNGAARDEN, I., and SOUDIGN, W., (1971). The absolute configuration and crystal structure of the anticholinergic drug dexbenzetimide. Nature, Lond., 232, 575 – 576.CrossRefGoogle Scholar
  25. 25.
    STEINER, G.W., and STRUBEL, G.A. (1971). Helminthosporoside, a host-specific toxin from Helminthosporium sacchari. J. biol. Chem., 246, 4348 – 4355.Google Scholar
  26. 26.
    STROMINGER, J.L. and BLUMBERG, P.M. (1974). Interaction of penicillin with the bacterial cell: Penicillin-binding proteins and penicillin-sensitive enzymes. Bact. Rev., 38, 291 – 335.PubMedGoogle Scholar
  27. 27.
    TEMPLETON, G.E. (1972). Altemaria toxins related to pathogenesis in plants. In: Microbial toxins. (Kadis, S., Ciegler, A. and AJL, S.J., Eds.). Vol. VIII. Fungal Toxins. 169 – 192. Academic Press, New York and London.Google Scholar
  28. 28.
    WOLFENDEN, R., (1972). Analog approaches to the structure of the transition state in enzymic reactions. Accts. Chem. Res., 5, 10 – 18.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1976

Authors and Affiliations

  • Daniel H. Rich
    • 1
  1. 1.School of PharmacyUniversity of WisconsinMadisonUSA

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