Jump to main content
Jump to site search

Issue 2, 2017
Previous Article Next Article

Linker-free incorporation of carbohydrates into in vitro displayed macrocyclic peptides

Author affiliations

Abstract

We report a strategy for efficient post-translational modification of a library of ribosomally-translated peptides by activation and elimination of cysteine to dehydroalanine then conjugate addition of a range of exogenous thiols, with an emphasis on carbohydrates. These reactions are selective for cysteine, and do not interfere with amplification of the nucleic acid component of an mRNA-displayed peptide. Furthermore, these reactions are shown to be compatible with two different macrocyclisation chemistries, and when applied to a peptide containing an N-terminal cysteine give a ketone that can be functionalised in an orthogonal manner. This new strategy can overcome a limitation of ribosomal translation, providing a means to incorporate untranslatable groups such as carbohydrates in amino acid side chains, and will allow for the ribosomal generation of glycopeptides, requiring only the introduction of a free thiol in the molecule to be incorporated. In combination with in vitro selection techniques, this strategy is envisaged to allow the discovery of biologically-active glycopeptides with a near-natural, but hydrolytically stable, thioglycosidic bond.

Graphical abstract: Linker-free incorporation of carbohydrates into in vitro displayed macrocyclic peptides

Back to tab navigation

Supplementary files

Publication details

The article was received on 01 Oct 2016, accepted on 18 Oct 2016 and first published on 21 Oct 2016


Article type: Edge Article
DOI: 10.1039/C6SC04381J
Citation: Chem. Sci., 2017,8, 1474-1481
  • Open access: Creative Commons BY license
  •   Request permissions

    Linker-free incorporation of carbohydrates into in vitro displayed macrocyclic peptides

    S. A. K. Jongkees, S. Umemoto and H. Suga, Chem. Sci., 2017, 8, 1474
    DOI: 10.1039/C6SC04381J

    This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. Material from this article can be used in other publications provided that the correct acknowledgement is given with the reproduced material.

    Reproduced material should be attributed as follows:

    • For reproduction of material from NJC:
      [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the Centre National de la Recherche Scientifique (CNRS) and the RSC.
    • For reproduction of material from PCCP:
      [Original citation] - Published by the PCCP Owner Societies.
    • For reproduction of material from PPS:
      [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the European Society for Photobiology, the European Photochemistry Association, and RSC.
    • For reproduction of material from all other RSC journals:
      [Original citation] - Published by The Royal Society of Chemistry.

    Information about reproducing material from RSC articles with different licences is available on our Permission Requests page.

Search articles by author

Spotlight

Advertisements