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 (NOGly) and l-α-hydrazinophenylalanine
(l-NNPhe) 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.