期刊
NATURE CHEMICAL BIOLOGY
卷 5, 期 12, 页码 888-890出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nchembio.259
关键词
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资金
- Japan Society for the Promotion of Science (JSPS) [16101007, 20-664, 19-1722]
- Japanese Industrial Science and Technology Program in the New Energy and Industrial Technology Development Organization (NEDO)
- Grants-in-Aid for Scientific Research [16101007] Funding Source: KAKEN
We report a methodology for the ribosomal synthesis of backbone-cyclized peptides involving genetic code reprogramming to introduce one or more nonproteinogenic amino acids. Expression of linear peptides bearing a cysteine-proline dipeptide sequence followed by glycolic acid results in self-rearrangement to a C-terminal diketopiperadine-thioester, which non-enzymatically generates a cyclized peptide. We demonstrate the ribosomal synthesis of several naturally occurring backbone-cyclized peptides and a library based on a bicyclic scaffold, and we identify bioactive sequences by screening and deconvolution.
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