Puromycin is an aminoacyl nucleoside antibiotic produced by Streptomyces alboniger. It is a broad spectrum, non-specific inhibitor of protein synthesis in Gram-positive bacteria, protozoans, and mammalian cells, including tumor cells, and is widely used as a key compound in various cell-free systems directed to elucidate the mechanism of protein synthesis and the mode of action of other inhibitors of this process. Puromycin is an analog for the 3' terminal of Tyr-tRNATyr which inhibits the enzyme peptidyl-transferase located in the 30s ribosomal subunits. Puromycin inhibits the enzyme by competition with aminoacyl-tRNA on the binding to the A' site or by attacking the peptidyl-tRNA in the P site of the enzyme. By this, the growing peptide chains on ribosomes are linked to the alpha-amino group of puromycin and interrupt the normal reaction of peptide bond formation.
Low levels of puromycin were found to act as an inhibitor of the soluble aminopeptidase (puromycin-sensitive aminopeptidase-PSA) in a variety of tissues. PSA inhibition by low puromycin concentrations that do not interfere with protein synthesis may directly lead to cell cycle arrest at the G2/M phase and induction of apoptosis. Cell Signaling Activators and Inhibitors, Apoptosis Inducers. Cell Signaling Activators and Inhibitors; Protein Synthesis and Transport Inhibitors.