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Selective N-terminal acylation of peptides and proteins with a Gly-His tag sequence

Author

Listed:
  • Manuel C. Martos-Maldonado

    (University of Copenhagen
    University of Copenhagen)

  • Christian T. Hjuler

    (University of Copenhagen
    University of Copenhagen)

  • Kasper K. Sørensen

    (University of Copenhagen
    University of Copenhagen)

  • Mikkel B. Thygesen

    (University of Copenhagen
    University of Copenhagen)

  • Jakob E. Rasmussen

    (University of Copenhagen
    University of Copenhagen)

  • Klaus Villadsen

    (University of Copenhagen
    University of Copenhagen)

  • Søren R. Midtgaard

    (University of Copenhagen)

  • Stefan Kol

    (Technical University of Denmark)

  • Sanne Schoffelen

    (University of Copenhagen
    University of Copenhagen)

  • Knud J. Jensen

    (University of Copenhagen
    University of Copenhagen)

Abstract

Methods for site-selective chemistry on proteins are in high demand for the synthesis of chemically modified biopharmaceuticals, as well as for applications in chemical biology, biosensors and more. Inadvertent N-terminal gluconoylation has been reported during expression of proteins with an N-terminal His tag. Here we report the development of this side-reaction into a general method for highly selective N-terminal acylation of proteins to introduce functional groups. We identify an optimized N-terminal sequence, GHHHn− for the reaction with gluconolactone and 4-methoxyphenyl esters as acylating agents, facilitating the introduction of functionalities in a highly selective and efficient manner. Azides, biotin or a fluorophore are introduced at the N-termini of four unrelated proteins by effective and selective acylation with the 4-methoxyphenyl esters. This Gly-Hisn tag adds the unique capability for highly selective N-terminal chemical acylation of expressed proteins. We anticipate that it can find wide application in chemical biology and for biopharmaceuticals.

Suggested Citation

  • Manuel C. Martos-Maldonado & Christian T. Hjuler & Kasper K. Sørensen & Mikkel B. Thygesen & Jakob E. Rasmussen & Klaus Villadsen & Søren R. Midtgaard & Stefan Kol & Sanne Schoffelen & Knud J. Jensen, 2018. "Selective N-terminal acylation of peptides and proteins with a Gly-His tag sequence," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05695-3
    DOI: 10.1038/s41467-018-05695-3
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    Cited by:

    1. Nathalie Ollivier & Magalie Sénéchal & Rémi Desmet & Benoît Snella & Vangelis Agouridas & Oleg Melnyk, 2022. "A biomimetic electrostatic assistance for guiding and promoting N-terminal protein chemical modification," Nature Communications, Nature, vol. 13(1), pages 1-10, December.

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