Abstract
In order to clarify the role of the guanido groups in streptomycin activity, derivatives of dihydrostreptomycin in which both guanido groups were replaced with either amino groups, ureido groups, or aminopyrimidine moieties were tested for their effects on streptomycin-sensitive, -resistant, and -dependent strains of Escherichia coli. In addition, a monoguanido derivative (bluensomycin), streptidine, and guanidine were tested.
The same order of effectiveness (streptomycin = dihydrostreptomycin > ureido derivative > aminopyrimidine derivative) was noted when inhibition of protein synthesis, effect on RNA and DNA synthesis, or loss of viability was determined in streptomycin-sensitive bacteria. In all cases there was a temporal relationship between cessation of protein synthesis and loss of viability. The amino derivative, streptidine, and guanidine were inactive.
In cell-free systems, using ribosomes from streptomycin-sensitive strains, the amino derivative had no effect on the polyuridylic acid-directed polymerization of phenylalanine. The aminopyrimidine and ureido derivatives were effective only at relatively higher concentrations.
Mutants selected for resistance to bluensomycin, dihydrostreptomycin, or the ureido derivative were resistant to all the derivatives. Strains selected for resistance to the aminopyrimidine derivative fell into two classes, one showing cross-resistance and the other sensitivity to dihydrostreptomycin and its derivatives.
- Copyright ©, 1969, by Academic Press Inc.
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