Jump to main content
Jump to site search

Issue 12, 2017
Previous Article Next Article

A benzylic linker promotes methyltransferase catalyzed norbornene transfer for rapid bioorthogonal tetrazine ligation

Author affiliations

Abstract

Site-specific alkylation of complex biomolecules is critical for late-stage product diversification as well as post-synthetic labeling and manipulation of proteins and nucleic acids. Promiscuous methyltransferases in combination with analogs of S-adenosyl-L-methionine (AdoMet) can functionalize all major classes of biomolecules. We show that benzylic moieties are transferred by Ecm1 with higher catalytic efficiency than the natural AdoMet. A relative specificity of up to 80% is achieved when a norbornene moiety is placed in para-position, enabling for the first time enzymatic norbornene transfer to specific positions in DNA and RNA— even in cell lysate. Subsequent tetrazine ligation of the stable norbornene moiety is fast, efficient, biocompatible and – in combination with an appropriate tetrazine – fluorogenic.

Graphical abstract: A benzylic linker promotes methyltransferase catalyzed norbornene transfer for rapid bioorthogonal tetrazine ligation

Back to tab navigation

Supplementary files

Publication details

The article was received on 18 Aug 2017, accepted on 09 Oct 2017 and first published on 10 Oct 2017


Article type: Edge Article
DOI: 10.1039/C7SC03631K
Citation: Chem. Sci., 2017,8, 7947-7953
  • Open access: Creative Commons BY-NC license
  •   Request permissions

    A benzylic linker promotes methyltransferase catalyzed norbornene transfer for rapid bioorthogonal tetrazine ligation

    F. Muttach, N. Muthmann, D. Reichert, L. Anhäuser and A. Rentmeister, Chem. Sci., 2017, 8, 7947
    DOI: 10.1039/C7SC03631K

    This article is licensed under a Creative Commons Attribution-NonCommercial 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 and it is not used for commercial purposes.

    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