Drug Receptor Interactions in Antimicrobial Chemotherapy: Symposium, Vienna, September 4-6, 1974

ISBN-13: 9783709184073 / Angielski / Miękka / 2012 / 314 str.

J. Drews; F. E. Hahn

Opis

The concept of chemotherapy as originated by Paul Ehrlich is based on the premise that antiparasitic drugs must have two properties: they must first bind to specific structures of the parasite which Ehrlich called chemoreceptors. Subsequent to their attachment to the chemoreceptor and by virtue of this binding they must possess the capacity to kill the parasite. Since the host which is to be cured of an invading parasite also contains a large number of chemoreceptors, that have the potential to bind toxic compounds, the task of the chemo therapist is to identify chemoreceptors of the parasite which are . not represented in the host and to design drugs which bind selectively to them In this context, Ehrlich called. for "the complete and exhaustive knowledge of all the different chemoreceptors of a certain parasite" as a "sine qua non for success in chemotherapy." Paradoxically and in spite of the fact that chemotherapy has become a very advanced and successful therapeutic discipline, few of its tri umphs have been achieved by following Ehrlich's original precepts. On the contrary, in the overwhelming majority of cases, effective drugs have been discovered without any knowledge of their chemoreceptors, and these drugs themselves have conversely been used as tools to study the nature of the chemoreceptors involved. In other words: chemother apy, notably antibacterial chemotherapy, has been successful without ever living up to the fundamental standards put forward by Paul Ehr lich."

Spis treści

I. Receptor Hypothesis.- Structure-Activity Rules and the Receptor Hypothesis.- Strategy of Drug-Design.- Physicochemical Factors in Drug-Receptor Interactions Demonstrated on the Example of the Sulfanilamides.- Quantitative Structure-Activity Relationships in Drug-Design.- II. DNA as a Drug-Receptor.- The Ecological Significance of R Factor Activity.- Structural Constraints in the Binding of Drugs to DNA.- Molecular Aspects of the Biosynthesis of R Factor DNA.- Elimination of Plasmidic Determinants by DNA-Complexing Compounds.- III. Ribosomes as Drug-Receptors.- Antibiotic Receptor-Sites in Escherichia coli Ribosomes.- Altered Methylation of Ribosomal RNA in Erythromycin-Resistant Staphylococcus Aureus.- Binding of Tetracyclines and Other Antibiotics to Ribosomes.- Ribosomal Effects of Thiostrepton and Related Antibiotics.- Studies on Active Sites of Ribosomes with Haloacetylated Antibiotic Analogs.- IV. The Mode of Action of Chloramphenicol.- Antibiotic Action on the Ribosomal Peptidyl Transferase Centre.- Experiments on the Binding Sites and the Action of Some Antibiotics which Inhibit Ribosomal Functions.- The Mode of Action of Pleuromutilin as Compared to Chloramphenicol.- A Structural Model of the Chloramphenicol Receptor Site.- V. Microbial Enzyme as Drug-Receptors.- Spin-Labelled Intermediates as Targets of Antibiotic Action in Peptidoglycan Synthesis.- Enzyme Inhibitors as Antimicrobial Agents.- Molecular Mechanism of Action of Rifamycins.- List of Participants.- List of Authors.