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Structure-Activity Rules and the Receptor Hypothesis

  • Fred E. Hahn
Conference paper
Part of the Topics in Infectious Diseases book series (TIDIS, volume 1)

Abstract

Chemotherapy as a science began with the postulation of the receptor hypothesis by Paul Ehrlich. His famous doctrine, corpora non agunt nisi fixata, substances do not act unless they are bound, should perhaps today be rephrased to say, corpora agunt quia fixata, substances do act because they are bound. Through much of his scientific life, Ehrlich propounded his embattled side chain theory in order to explain the interaction of chemotherapeutic drugs with bioreceptors which were still hypothetical. Ehrlich’s early observations of vital staining offered the first visible evidence of selective binding of chemicals to bioreceptors, and his demonstration, in 1891 (Guttmann and Ehrlich, 1891), of the therapeutic value of methylene blue in the treatment of vivax malaria was directly based upon the selective staining properties of this dye for malarial parasites.

Keywords

Double Helix Vivax Malaria Scatchard Plot Hill Plot Alanine Racemase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Albert, A., S.D. Rubbo and M.I. Burvill: The influence of chemical constitution on antibacterial activity. Part IV: A survey of heterocyclic bases with special reference to benzquinolines, phenanthridines, benzacridines, quinolines and pyridines. Brit. J. Exp. Path. 30, 159 (1949).PubMedGoogle Scholar
  2. Ciak, J. and F.E. Hahn: Mechanisms of action of antibiotics. II. Studies on the modes of action of cycloserine and its L-stereoisomer. Antibiotics & Chemother. 9, 47 (1958).Google Scholar
  3. Fildes, P. and M.B. Camb: A rational approach to research in chemotherapy. Lancet 1, 955 (1940).CrossRefGoogle Scholar
  4. Guttmann, P. and P. Ehrlich: Ober die Wirkung des Methylenblau bei Malaria. Berl. Klin. Wochenschr. 28, 953 (1891).Google Scholar
  5. Hahn, F.E.: Complexes of biologically active substances with nucleic acids - yesterday, today, tomorrow. Progr. Mol. Subcell. Biol. 2, 1 (1971) Springer, Berlin-Heidelberg-New York.Google Scholar
  6. Hahn, F.E.: Distamycin A and Netropsin. In Antibiotics III. J. Corcoran and F.E. Hahn edts. Springer, Berlin-Heidelberg-New York, 1974, p 79.Google Scholar
  7. Hahn, F.E., R.L. O’Brien, J. Ciak, J.L. Allison and J.G. Olenick: Studies on modes of action of chloroquine, quinacrine and quinine and on chloroquine resistance. Military Med. 131, 1071 (1966).Google Scholar
  8. Hopps, H.E., C.L. Wisseman, F.E. Hahn, J.E. Smadel and R. Ho: Mode of action of chloramphenicol. IV. Failure of selected natural metabolites to reverse antibiotic action. J. Bact. 72, 561 (1956).PubMedCrossRefGoogle Scholar
  9. Krey, A.K. and F.E. Hahn: Optical studies on the interaction of DL-quinacrine with double-and single-stranded calf thymus DNA. Molecular Pharmacol. 10, in press (1974).Google Scholar
  10. Lerman, L.S.: The structure of the DNA-acridine complex. Proc. Nat. Acad. Sci. USA 49, 94 (1963).PubMedCrossRefGoogle Scholar
  11. Lerman, L.S.: Acridine mutagens and DNA structure. J. Cell. Comp. Physiol. 64, Suppl 1, 1 (1964).CrossRefGoogle Scholar
  12. Nathans, D.: Puromycin inhibition of protein synthesis: The incorporation of puromycin into peptide chains. Proc. Nat. Acad. Sci. USA 51, 585 (1964).PubMedCrossRefGoogle Scholar
  13. Newton, B.A.: A fluorescent derivative of polymyxin: Its preparation and use in studying the site of action of the antibiotic. J. Gen. Microbiol. 12, 226 (1955).PubMedGoogle Scholar
  14. Newton, B.A.: Interaction of berenil with deoxyribonucleic acid and some. characteristics of the berenil-deoxyribonucleic acid complex. Biochem. J. 105, 50 p (1967).Google Scholar
  15. Newton, B.A. and R.W.F. LePage: Preferential inhibition of extranuclear deoxyribonucleic acid synthesis by the trypanocide berenil. Biochem. J. 105, 50 p (1967).Google Scholar
  16. Nierhaus, D. and K.H. Nierhaus: Identification of chloramphenicol-bindingprotein in Escherichia coli ribosomes by partial reconstitution. Proc. Nat. Acadprotein in Escherichia coli ribosomes by partial reconstitution. Proc. Nat. Acad. Sci. USA 70, 2224 1973 ).Google Scholar
  17. Pachmann, U. and R. Rigler: Quantum yield of acridines interacting with DNA of defined base sequence. Expt. Cell Res. 72, 602 (1972).CrossRefGoogle Scholar
  18. Prusoff, W.H., Y.S. Bakhle and J.F. McCrea: Incorporation of 5-iodo-2’-deoxyuridine into the deoxyribonucleic acid of vaccinia virus. Nature 199, 1310 (1963).PubMedCrossRefGoogle Scholar
  19. Strominger, J.L.: Antibiotics as inhibitors of bacterial cell-wall synthesis. Antimicrobial Agents Annual 1960, 328 (1961).Google Scholar
  20. Szybalski, W. and V.N. Iyer: The mitomycins and porfiromycins. In Antibiotics I, D. Gottlieb and P.D. Shaw edts. Springer, Berlin-Heidelberg-New York, 1967, p 211.Google Scholar
  21. Thomas, J.C., G. Weill and M. Daune: Fluorescence of proflavine-DNA complexes: Heterogeneity of binding sites. Biopolymers 8, 647 (1969).CrossRefGoogle Scholar
  22. Watson, J.D. and F.H.C. Crick: The structure of DNA. Cold Spring Harb. Symp. Quant. Biol. 18, 123 (1953).CrossRefGoogle Scholar
  23. Wolfe, A.D. and F.E. Hahn: Mode of action of chloramphenicol. IX. Effects of chloramphenicol upon a ribosomal amino acid polymerization system and its binding to bacterial ribosomes. Biochim. Biophys. Acta 95, 146 (1965).PubMedGoogle Scholar

Copyright information

© Springer-Verlag/Wien 1975

Authors and Affiliations

  • Fred E. Hahn

There are no affiliations available

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