Mode of action of macrolides

Abstract

1. 1. The eight macrolides studied have a similar mode of action. They inhibit protein synthesis by interfering with the binding of aminoacyl-tRNA to ribosomes. They do not inhibit the activation of amino acid, the formation of aminoacyl-tRNA, the attachment of mRNA to ribosomes or the reassociation of 30-S and 50-S ribosomal subunits. 2. 2. Varying the concentrations of Mg 2+ or poly-U has no effect on the extent of inhibition of protein synthesis by erythromycin. 3. 3. Erythromycin and oleandomycin inhibit protein synthesis to a greater degree in alkaline solutions than in acidic solutions. It is therefore proposed that the non-protonated molecules are the active species. 4. 4. The low-p K macrolides inhibit both aminoacyl-tRNA and peptidyl-tRNA binding to ribosomes. The high-p K macrolides probably inhibit only peptidyl-tRNA binding.