A Small-Molecule-Based Approach to Sense Codon-Templated Natural-Unnatural Hybrid Peptides. Selective Silencing and Reassignment of the Sense Codon by Orthogonal Reacylation Stalling at the Single-Cod

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• 作者：Shinsuke Sando ; Keiichiro Kanatani ; Nobuhiko Sato ; Hironori Matsumoto ; Takahiro Hohsaka ; and Yasuhiro Aoyama
• 刊名：Journal of the American Chemical Society
• 出版年：2005
• 出版时间：June 8, 2005
• 年：2005
• 卷：127
• 期：22
• 页码：7998 - 7999
• 全文大小：63K
• 年卷期：v.127,no.22(June 8, 2005)
• ISSN：1520-5126

文摘

In the presence of the stable sulfamoyl analogue of phenylalanyl adenylate (Phe-SA), the UUU/UUC sense codon for phenylalanine (Phe) can be silenced and reassigned to a naphthylalanine (Nap) conjugated to tRNA^Phe. We have demonstrated the efficiency and selectivity or orthogonality of the Phe-to-Nap reassignment induced by an "orthogonal reacylation stalling" strategy at the single-codon level in the translation of mRNAs of dihydrofolate reductase and a 24-mer oligopeptide. We used a prokaryotic translation system with an essential preincubation, during which the endogenous precharged phenylalanyl-tRNA^Phe undergoes deacylation and the reacylation of the resulting tRNA^Phe is stalled by the action of Phe-SA to inhibit the phenylalanyl-tRNA synthetase activity. We discuss the significance of the present small-molecule-based approach to sense-codon templated natural-unnatural peptides.