The Mechanism by which Cycloheximide and Related Glutarimide Antibiotics Inhibit Peptide Synthesis on Reticulocyte Ribosomes

Cycloheximide and related glutarimide antibiotics have been shown to affect binding, transfer enzyme II-dependent movement, and release of transfer RNA from the donor site of reticulocyte ribosomes, as well as both the initiation and extension of globin and phenylalanine peptides. They inhibit binding of deacylated tRNAphe to reticulocyte ribosomes in the absence of transfer enzymes at concentrations similar to those that inhibit peptide initiation. These concentrations are below those required for comparable inhibition of peptide extension or transfer enzyme II-dependent translocation of peptidyl-tRNA from the acceptor to the donor ribosomal sites and appear to provide the basis for differential inhibition of peptide initiation and extension.