Inhibition of ribosomal translocation by peptidyl-tRNA analogs

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Abstract
The activity of peptidyl-tRNALys-CpCp2''dA was measured in an in vitro poly(A)-dependent polypeptide synthesizing system derived from Escherichia coli. It has already been shown that Lys-tRNALys-CpCp2''dA is active as an acceptor and Ac2-Lys-tRNALys-CpCp2''dA can donate its peptidyl residue but that the overall poly(A)-dependent synthesis of polylysine does not take place with Lys-tRNALys-CpCp2''dA. This is due to the efficient inhibition of the EF[elongation factor]-G-dependent translocation of the peptidyl-tRNA-CpCp2''dA from the ribosomal A to the ribosomal P site. In addition, the EF-G-dependent release of the deacylated tRNALys-CpCp2''dA from the ribosomes is also inhibited. The action of the EF-G or some other ribosomal component participating in the translocation process requires the presence of the 2''-hydroxyl group on the terminal adenosine of tRNA. If this hydroxyl group is not present on the tRNA, the ribosomes remain locked in their pretranslocational state.