Diverse backbone-cyclized peptides via codon reprogramming.
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.
Kawakami
Takashi
T
Department of Chemistry and Biotechnology, The University of Tokyo, Japan.
Ohta
Atsushi
A
Ohuchi
Masaki
M
Ashigai
Hiroshi
H
Murakami
Hiroshi
H
Suga
Hiroaki
H
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000235:genetics; D003062:Codon / Q000235:genetics*; D008969:Molecular Sequence Data; D010452:Peptide Biosynthesis; D019151:Peptide Library; D010456:Peptides, Cyclic / Q000096:biosynthesis / Q000138:chemical synthesis* / Q000737:chemistry / Q000235:genetics; D011487:Protein Conformation; D012333:RNA, Messenger / Q000235:genetics; D012343:RNA, Transfer / Q000235:genetics; D011995:Recombination, Genetic; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism; D013698:Templates, Genetic
D000596:Amino Acids; D003062:Codon; D019151:Peptide Library; D010456:Peptides, Cyclic; D012333:RNA, Messenger; D012343:RNA, Transfer