Cover Picture: Ribosomal Synthesis of Backbone-Macrocyclic Peptides Containing γ-Amino Acids (ChemBioChem 8/2011)

Authors

  • Yukinori Ohshiro,

    1. Department of Advanced Interdisciplinary Studies, Graduate School of Engineering, The University of Tokyo, 4-6-1, Komaba, Meguro, Tokyo 153-8904 (Japan)
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  • Dr. Eiji Nakajima,

    1. Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1, Hongo, Bunkyo, Tokyo 113-8656 (Japan)
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  • Dr. Yuki Goto,

    1. Department of Chemistry, Graduate School of Science, The University of Tokyo, 7-3-1, Hongo, Bunkyo, Tokyo 113-0033 (Japan), Fax: (+81) 3-5841-8372
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  • Dr. Shinichiro Fuse,

    1. Department of Applied Chemistry, Tokyo Institute of Technology, 2-12-1, Ookayama, Meguro, Tokyo 152-8552 (Japan)
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  • Prof. Dr. Takashi Takahashi,

    1. Department of Applied Chemistry, Tokyo Institute of Technology, 2-12-1, Ookayama, Meguro, Tokyo 152-8552 (Japan)
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  • Prof. Dr. Takayuki Doi,

    1. Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3, Aza-aoba, Aramaki, Aoba, Sendai, Miyagi 980-8578 (Japan)
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  • Prof. Dr. Hiroaki Suga

    Corresponding author
    1. Department of Chemistry, Graduate School of Science, The University of Tokyo, 7-3-1, Hongo, Bunkyo, Tokyo 113-0033 (Japan), Fax: (+81) 3-5841-8372
    2. Department of Advanced Interdisciplinary Studies, Graduate School of Engineering, The University of Tokyo, 4-6-1, Komaba, Meguro, Tokyo 153-8904 (Japan)
    3. Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1, Hongo, Bunkyo, Tokyo 113-8656 (Japan)
    4. WCU Department of Molecular Medicine and Biopharmaceutical Sciences, Seoul National University, Seoul 151-742 (Korea)
    • Department of Chemistry, Graduate School of Science, The University of Tokyo, 7-3-1, Hongo, Bunkyo, Tokyo 113-0033 (Japan), Fax: (+81) 3-5841-8372
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Abstract

original image

The cover picture shows ribosomal synthesis of backbone macrocyclic peptides containing γ-amino acids. γ-Amino acids are notoriously difficult to incorporate into a peptide chain by elongation, but this work gets around the problem by initiating the translation using γ-aminoacyl-phenylalanine (γaa-F) dipeptides, and cyclizing the backbone. Because the N-terminal γ-amino group and the carbonyl of the C-terminal residue were ligated via a peptide bond, the γ-amino acid is embedded in the middle of sequence of peptide chain. To cyclize the backbone, genetic code reprogramming was used to install a sequence of cystidyl-prolyl-glycolate (C-P-HOG), which self-rearranges into a diketopiperadine (dkp) thioester and spontaneously macrocyclizes via the nucleophilic attack of the N-terminal γ-amino group to the dkp-thioester. In the background is the tertiary structure of a tRNA–flexizyme (a critical enzyme used for the preparation of γaa-F-tRNA as well as HOG-tRNA) complex. This illustration was created by Y. Goto with valuable suggestions from K. Futai. For more information see the paper by H. Suga et al. on p. 1183 ff.

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