Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Amino Acids / genetics
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Codon / genetics*
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Molecular Sequence Data
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Peptide Biosynthesis*
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Peptide Library
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Peptides, Cyclic / biosynthesis
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Peptides, Cyclic / chemical synthesis*
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Peptides, Cyclic / chemistry
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Peptides, Cyclic / genetics
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Protein Conformation
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RNA, Messenger / genetics
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RNA, Transfer / genetics
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Recombination, Genetic
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Ribosomes* / genetics
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Ribosomes* / metabolism
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Templates, Genetic
Substances
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Amino Acids
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Codon
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Peptide Library
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Peptides, Cyclic
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RNA, Messenger
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RNA, Transfer
Associated data
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PubChem-Substance/85244535
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PubChem-Substance/85244536
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PubChem-Substance/85244537
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PubChem-Substance/85244538
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PubChem-Substance/85244539
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PubChem-Substance/85244540
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PubChem-Substance/85244541
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PubChem-Substance/85244542
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PubChem-Substance/85244543
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PubChem-Substance/85244544
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PubChem-Substance/85244545
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PubChem-Substance/85244546
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PubChem-Substance/85244547
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PubChem-Substance/85244548
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PubChem-Substance/85244549
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PubChem-Substance/85244550
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PubChem-Substance/85244551