Ribosomal Elongation of Cyclic γ-Amino Acids using a Reprogrammed Genetic Code.
J Am Chem Soc
; 142(11): 4965-4969, 2020 03 18.
Article
em En
| MEDLINE
| ID: mdl-32129615
ABSTRACT
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 the best of our knowledge. To avoid such self-cyclization, we utilized cyclic γ-amino acids and demonstrated their elongation into a peptide chain. Although the incorporation of the cyclic γ-amino acids is intrinsically slow, we here show 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 ß-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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1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oligopeptídeos
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Elongação Traducional da Cadeia Peptídica
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Peptídeos Cíclicos
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Ribossomos
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Código Genético
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Aminoácidos Cíclicos
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article