Consecutive Ribosomal Incorporation of α-Aminoxy/α-Hydrazino Acids with l/d-Configurations into Nascent Peptide Chains.

α-Aminoxy and α-hydrazino acids are β-amino acid analogs with β-carbons replaced by oxygen and nitrogen, respectively. Such heteroatoms dictate the folding of peptides into specific secondary structures called pseudo-γ-turns. Achiral α-aminoxyacetic acid (Gly) and l-α-hydrazinophenylalanine (l-Phe) have been shown to be suitable for single incorporation during ribosomal translation, but whether ribosomes tolerate other types of α-aminoxy/α-hydrazino acids with l/d-configurations is unknown. Moreover, whether multiple or consecutive incorporations are possible remains unclear. We show, for the first time, multiple and consecutive incorporations of α-aminoxy/α-hydrazino acids with l/d-configurations into various model peptides, including macrocyclic peptide scaffolds.