Inhibitors aminoacyl-tRNA binding

Grp, Group antibiotic group specificity A, inhibitors of aminoacyl—tRNA binding B, inhibitors of peptide bond formation C, inhibitors of translocation. 

After formation of the initiation dipeptide, the first EF-G-dependent translocation allows binding of the third aminoacyl-tRNA in the A-site so that a tripeptide is formed. The apparent rate of this event may depend upon the nature of the initiation complex initially formed, being slower, for instance, with those containing mRNAs with an extended SD sequence than with those having either very short or no SD complementarity (C. O. G. and M. Rodnina, unpublished results). Furthermore, very powerful translocation inhibitors may block tripeptide formation to such an extent that they mimic translation initiation inhibitors. 

The three antibiotic inhibitors of translation that will be used in this experiment are chloramphenicol, cycloheximide, and puromycin (Fig. 23-10). Chloramphenicol is specific for prokaryotic ribosomes, blocking the transfer of the peptide on the tRNA at the P site to the amino acid linked to the tRNA at the A site (the peptidyl transfer reaction). Since the source of the ribosomes used in this experiment is wheat germ (eukaryotic), we would predict that chloramphenicol would not have a great effect on translation. The mechanism of cycloheximide-mediated inhibition is the same as that described above for chloramphenicol, except for the fact that it is specific for the 80S eukaryotic ribosome. Puromycin is a more broad translational inhibitor, effective on both eukaryotic and prokaryotic ribosomes. It acts as a substrate analog of aminoacyl tRNA. When it binds at the A site of the ribosome, it induces premature termination of translation (Fig. 

Inhibitor of the binding of aminoacyl-tRNA, used in agriculture (treatment of rice blast disease)... 

Vazquez, D. and Monro, R. E. (1967) Effects of some inhibitors of protein synthesis on the binding of aminoacyl-tRNA to ribosomal subunits. Biochim. Biophys. Acta, 142,155-173. 

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