Abstract
Effects of blasticidin S, a nucleoside antibiotic of structural similarity with puromycin, on protein synthetic pathways was studied stepwise to determine the site of action of the antibiotic in a bacterial system. Blasticidin S markedly inhibited leucine incorporation into polypeptides under the direction of endogenous messengers in extracts of E. coli and B. megaterium. No inhibition by the antibiotic of oxidative phosphorylation was detected. Without interfering with formation of amino-acyl-sRNA, it blocked the transfer of leucine from leucyl-sRNA to polypeptides to the extent enough to account for the inhibition of free leucine incorporation into polypeptides. Unlike puromycin, blasticidin S reduced the release of peptides from the ribosome to the supernatant. It inhibited poly U-directed polyphenylalanine synthesis to the degree as high as that of the inhibition of leucine incorporation into polypeptides under the direction of natural messengers. It was suggested that the antibiotic attacked a certain steps following the formation of active complexes of ribosomes and messenger strands. Blasticidin S also inhibited leucine incorporation into poly-peptides in cell-free systems of mammalian cells, more highly in a system of mouse Ehrlich carcinoma than in that of normal rat liver.
This investigation was supported in whole by Public Health Service Researdh Grant CA05082-04, from the U. S. National Cancer Institute.
