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Aminoglycoside antibiotics were found to vary widely in the effect of variation in their concentration on the degree of misreading of synthetic RNA messengers. Thus, neomycin, kanamycin, and gentamicin showed a 3- to 5-fold increase in the level of misreading as the drug concentration was raised from 10−6 to 10−4M. This effect suggests that each of these drugs may act on more than one site. Observed changes in the qualitative nature of the misreading at different concentrations support this inference, which is also consistent with the absence of one-step mutants with high level resistance to these drugs. In contrast, little increase in misreading, over the same concentration range, was seen with streptomycin and paromomycin, for which one-step, high level, resistant mutants are known. It therefore seems that these drugs each act on only a single site.
Davies et al. (Sat,) studied this question.