IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v562y2018i7728d10.1038_s41586-018-0608-y.html
   My bibliography  Save this article

A protein functionalization platform based on selective reactions at methionine residues

Author

Listed:
  • Michael T. Taylor

    (University of Cambridge)

  • Jennifer E. Nelson

    (University of Cambridge)

  • Marcos G. Suero

    (University of Cambridge)

  • Matthew J. Gaunt

    (University of Cambridge)

Abstract

Nature has a remarkable ability to carry out site-selective post-translational modification of proteins, therefore enabling a marked increase in their functional diversity1. Inspired by this, chemical tools have been developed for the synthetic manipulation of protein structure and function, and have become essential to the continued advancement of chemical biology, molecular biology and medicine. However, the number of chemical transformations that are suitable for effective protein functionalization is limited, because the stringent demands inherent to biological systems preclude the applicability of many potential processes2. These chemical transformations often need to be selective at a single site on a protein, proceed with very fast reaction rates, operate under biologically ambient conditions and should provide homogeneous products with near-perfect conversion2–7. Although many bioconjugation methods exist at cysteine, lysine and tyrosine, a method targeting a less-explored amino acid would considerably expand the protein functionalization toolbox. Here we report the development of a multifaceted approach to protein functionalization based on chemoselective labelling at methionine residues. By exploiting the electrophilic reactivity of a bespoke hypervalent iodine reagent, the S-Me group in the side chain of methionine can be targeted. The bioconjugation reaction is fast, selective, operates at low-micromolar concentrations and is complementary to existing bioconjugation strategies. Moreover, it produces a protein conjugate that is itself a high-energy intermediate with reactive properties and can serve as a platform for the development of secondary, visible-light-mediated bioorthogonal protein functionalization processes. The merger of these approaches provides a versatile platform for the development of distinct transformations that deliver information-rich protein conjugates directly from the native biomacromolecules.

Suggested Citation

  • Michael T. Taylor & Jennifer E. Nelson & Marcos G. Suero & Matthew J. Gaunt, 2018. "A protein functionalization platform based on selective reactions at methionine residues," Nature, Nature, vol. 562(7728), pages 563-568, October.
  • Handle: RePEc:nat:nature:v:562:y:2018:i:7728:d:10.1038_s41586-018-0608-y
    DOI: 10.1038/s41586-018-0608-y
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41586-018-0608-y
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.

    File URL: https://libkey.io/10.1038/s41586-018-0608-y?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Mengzhun Guo & Kai Zhao & Liang Guo & Rui Zhou & Qiuju He & Kuan Lu & Tian Li & Dandan Liu & Jinfeng Chen & Jing Tang & Xin Fu & Jinyun Zhou & Bei Zheng & Samuel I. Mann & Yongdeng Zhang & Jing Huang , 2023. "Copper assisted sequence-specific chemical protein conjugation at a single backbone amide," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    2. Luke J. Dowman & Sameer S. Kulkarni & Juan V. Alegre-Requena & Andrew M. Giltrap & Alexander R. Norman & Ashish Sharma & Liliana C. Gallegos & Angus S. Mackay & Adarshi P. Welegedara & Emma E. Watson , 2022. "Site-selective photocatalytic functionalization of peptides and proteins at selenocysteine," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    3. Samrat Sahu & Benjamin Emenike & Christian Michel Beusch & Pritha Bagchi & David Ezra Gordon & Monika Raj, 2024. "Copper(I)-nitrene platform for chemoproteomic profiling of methionine," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:562:y:2018:i:7728:d:10.1038_s41586-018-0608-y. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.