Reflecting recent work in the Suga lab

Because γ-amino acids generally undergo rapid self-cyclization upon esterification on the carboxyl group, for example, γ-aminoacyl-tRNA, there are no reports of the ribosomal elongation of γ-amino acids. To avoid such self-cyclization, researchers in the Suga lab utilized cyclic γ-amino acids and demonstrate their elongation into a peptide chain.

Although the incorporation of the cyclic γ-amino acids is intrinsically slow, they have shown that the combination of elongation factor P and engineered tRNAs improves cyclic γ-amino acid incorporation efficiency. Via this method, thioether-macrocyclic peptides containing not only cyclic γ-amino acids but also d-α-, N-methyl-α-, and cyclic β-amino acids were expressed under the reprogrammed genetic code.

Ribosomally synthesized macrocyclic peptide libraries containing cyclic γ-amino acids should be applicable to in vitro screening methodologies such as mRNA display for discovering novel peptide drugs.

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