Structure-Activity Rules and the Receptor Hypothesis
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.
KeywordsDouble Helix Vivax Malaria Scatchard Plot Hill Plot Alanine Racemase
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- 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
- 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
- Guttmann, P. and P. Ehrlich: Ober die Wirkung des Methylenblau bei Malaria. Berl. Klin. Wochenschr. 28, 953 (1891).Google Scholar
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- Strominger, J.L.: Antibiotics as inhibitors of bacterial cell-wall synthesis. Antimicrobial Agents Annual 1960, 328 (1961).Google Scholar
- 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