© 2005 Oxford University Press
Ribosome-catalyzed synthesis of protein/oligopeptides with unnatural backbone
Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering Kyoto University, Katsura, Nishikyo-ku, Kyoto 615-8510, Japan
Nonsense suppression method was used to probe the allowable modification of substrate (amino acid) backbone in the prokaryotic ribosomal system. Dihydrofolate reductase (DHFR) with an amber mutation was translated in the RF1-diminished prokaryotic cell free translation system in the presence of chemically-misacylated yeast tRNAPheCUA. The prokaryotic ribosome showed a restricted tolerance to the backbone modification. Although natural-type 
-amino acid was accepted as a good substrate for the ribosome, incorporation of ß-aminopropionic acid was not detected under our experimental conditions. Interestingly, we found that the homologous ß-hydroxyalkanoic acid with elongated methylene (backbone) chain-length can be a substrate for the ribosome, giving an important implication for the chemical mechanism of the ribosome-catalyzed peptide bond forming reaction.