Kanamycin and streptomycin belong to a group of basic glycoside antibiotics and the biological activities are similar. A number of investigations, concerning the mechanism of action of these antibiotics have been performed. They include effects on or by aerobic respiration1~5), a damage of cytoplasmic membrane6~17), a reaction with nucleic acids18, 19) or an inhibition of protein synthesis20~25).
Erdös and Ullman20, 21) revealed that streptomycin inhibits the incorporation of 14Camino acids into protein in a cell-free system from a strain of Mycobacterium. Flaks et al.24,25) observed an inhibition of polyphenylalanine synthesis by streptomycin, using a cell-free amino acid incorporating system from E.coli. The 14C-phenylalanine incorporation, stimulated by polyuridylate, was inhibited by the presence of streptomycin. They concluded that the inhibition of polypeptide synthesis is due to binding of streptomycin to the ribosome, and an origin of streptomycin resistance is located in the ribosome. Later it was revealed that streptomycin does not interfere with the attachment of polyuridylate to the ribosome.32 ,33) Rosenkranz26) reported that a strain of E. coli, carrying an episome for multiple drug resistance (the resistance transfer factor), has decreased permeability for streptomycin.
An inhibition of protein synthesis by kanamycin was observed in the previous study23). Tanaka et al.27) studied with a kanamycin-resistant mutant of E. coli, and found that resistant changes are located in the ribosome. It was concluded that the primary site of action may be the ribosome. They observed one-way cross resistance in leucine incorporation into protein with the ribosomes and native messengers from streptomycin-resistant and kanamycin-resistant mutants as in the case of growth-inhibitory activity. However, no cross resistance was demonstrated with polyphenylalanine synthesis, which is dependent on a synthetic messenger, polyuridylate. It suggested that the binding site of kanamycin is different from that of streptomycin on the ribosome.
For the purpose of elucidating the detailed site of action of kanamycin on protein synthesis, studies were performed with a cell-free system from E. coli and rat liver, with particular reference to the selective toxicity. The results are presented in this publication.
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