期刊
CHEMBIOCHEM
卷 10, 期 7, 页码 1186-1192出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbic.200900058
关键词
genetic code; peptidomimics; protein engineering; ribosomal synthesis; ribozymes
资金
- New Energy and Industrial Technology Development Organization (NEDO)
- Japan Society for the Promotion of Science [16107007]
- Global COE Program Chemistry Innovation through Cooperation of Science and Engineering
- MEXT Japan
- Grants-in-Aid for Scientific Research [16107007] Funding Source: KAKEN
The C terminus of a peptide expressed by the translation apparatus generally ends in a carboxylate group. On the other hand, the C termini of some naturally occuring peptides have amide moieties instead of carboxylates, which are believed to give better biostability. Here, we describe a new strategy for the ribosomal synthesis of peptides featuring C-terminal lactam, thiolactone, and alkylamide units. The method was based on the concept of genetic code reprogramming involving the flexizymes (flexible tRNA acylation ribozymes) and the PURE (peptide synthesis using recombinant elements) system, in which vacant codons are reassingned to nonproteinogenic amino acids, this enabled us to convert the C termini of peptides into the above functionalities. We have also applied this method to the synthesis of a macrocyclic peptide closed by an amide bond formed between a lysine side chain and the peptide C terminus. This method thus offers us new opportunities to express various peptides using the translation apparatus, and potentially to accelerate the discovery of peptide drugs designed for various therapeutic targets.
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