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The mechanism of inhibition of Escherichia coli by the new nucleoside antibiotic, 2'-amino-2'-deoxyguanosine (2AG), is described. Upon the addition of 2AG, the syntheses of macromolecules continued for 15 minutes. After this lag time, protein synthesis sharply decreased, Rna synthesis slightly decreased, but DNA synthesis was not affected. Tritiated 2AG was readily incorporated into the acid-soluble fraction of cells in the form of the mono-, di- and triphosphates. In the acid-soluble fraction, radioactivity was found only in the RNA fraction. The major part of the radioactivity was found to be guanylate; only 25% existed as the nucleotide of 2AG. In resistant strains of E. coli, there was a lower degree of phosphorylating activity and less incorporation of 2AG into RNA per unit of cell mass increase. These results suggest that 2AG inhibits growth by its incorporation into RNA and the subsequent distrubance of RNA function causing a block in protein synthesis.

Mechanism of growth inhibition by 2'-amino-2'-deoxyguanosine in Escherichia coli.