title: A simple approach to sense codon-templated synthesis of natural/unnatural hybrid peptides.
abstract: In the presence of Phe-SA, the stable sulfamoyl analogue of phenylalanyl adenylate, the codon (UUU/UUC) for phenylalanine (Phe) can be reassigned to naphthylalanine (Nap) bound to tRNA(Phe). The efficiency and selectivity of this Phe-to-Nap reassignment induced by the "orthogonal reacylation stalling" method was demonstrated at the single-codon level in the translation of mRNAs of dihydrofolate reductase (DHFR) and a 24-mer oligopeptide. In the prokaryotic translation system with essential preincubation, the endogenous precharged phenylalanyl-tRNA(Phe) undergoes deacylation and reacylation of the resulting tRNA(Phe) is inhibited by the action of Phe-SA to kill the phenylalanyl-tRNA synthetase activity. The significance of the present small-molecule-based approach to sense-codon templated natural-unnatural peptides is discussed.
authors.affiliation: Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto 615-8510, Japan.
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Kanatani
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Sando
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Aoyama
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D000409:Alanine / Q000031:analogs & derivatives / Q000737:chemistry; D001483:Base Sequence; D003062:Codon; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009281:Naphthalenes / Q000737:chemistry; D010455:Peptides / Q000737:chemistry; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D010652:Phenylalanine-tRNA Ligase / Q000037:antagonists & inhibitors*; D014176:Protein Biosynthesis; D015202:Protein Engineering; D012360:RNA, Transfer, Phe / Q000737:chemistry; D013698:Templates, Genetic; D013762:Tetrahydrofolate Dehydrogenase / Q000096:biosynthesis / Q000235:genetics
chemical_list: C520214:5'-O-(N-(phenylalanyl)sulfamoyl)adenosine; D003062:Codon; D004791:Enzyme Inhibitors; D009281:Naphthalenes; D010455:Peptides; D012360:RNA, Transfer, Phe; D010649:Phenylalanine; D013762:Tetrahydrofolate Dehydrogenase; D010652:Phenylalanine-tRNA Ligase; D000241:Adenosine; D000409:Alanine; C513002:2-naphthylalanine