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Discovery of Functional Macrocyclic Peptides by Means of the RaPID System

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Cyclic Peptide Design

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2001))

Abstract

Flexizymes, highly flexible tRNA aminoacylation ribozymes, have enabled charging of virtually any amino acid (including non-proteogenic ones) onto tRNA molecules. Coupling to a custom-made in vitro translation system, namely the flexible in vitro translation (FIT) system, has unveiled the remarkable tolerance of the ribosome toward molecules, remote from what nature has selected to carry out its elaborate functions. Among the very diverse molecules and chemistries that have been ribosomally incorporated, a plethora of entities capable of mediating intramolecular cyclization have revolutionized the design and discovery of macrocyclic peptides. These macrocyclization reactions (which can be spontaneous, chemical, or enzymatic) have all served as tools for the discovery of peptides with natural-like structures and properties. Coupling of the FIT system and mRNA display techniques, known as the random non-standard peptide integrated discovery (RaPID) system, has in turn allowed for the simultaneous screening of trillions of macrocyclic peptides against challenging biological targets. The macrocyclization methodologies are chosen depending on the structural and functional characteristics of the desired molecule. Thus, they can emanate from the peptide’s N-terminus or its side chains, attributing flexibility or rigidity, or even result in the installation of fluorescent probes.

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Author information

Author notes

  1. Christos Tsiamantas, Manuel E. Otero-Ramirez, and Hiroaki Suga contributed equally to this work.

Authors and Affiliations

  1. Department of Chemistry, Graduate School of Science, The University of Tokyo, Bunkyo, Tokyo, Japan

    Christos Tsiamantas, Manuel E. Otero-Ramirez & Hiroaki Suga

Authors
  1. Christos Tsiamantas
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  2. Manuel E. Otero-Ramirez
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  3. Hiroaki Suga
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Corresponding author

Correspondence to Hiroaki Suga .

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Editors and Affiliations

  1. Hit Discovery and Optimization, Pfizer R&D, Groton, CT, USA

    Gilles Goetz

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Tsiamantas, C., Otero-Ramirez, M.E., Suga, H. (2019). Discovery of Functional Macrocyclic Peptides by Means of the RaPID System. In: Goetz, G. (eds) Cyclic Peptide Design. Methods in Molecular Biology, vol 2001. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9504-2_14

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  • DOI: https://doi.org/10.1007/978-1-4939-9504-2_14

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-4939-9503-5

  • Online ISBN: 978-1-4939-9504-2

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