Electrochemical Modification of Polypeptides at Selenocysteine

Angus S. Mackay, Joshua W.C. Maxwell, Max J. Bedding, Sameer S. Kulkarni, Stephen A. Byrne, Lucas Kambanis, Mihai V. Popescu, Robert S. Paton, Lara R. Malins, Anneliese S. Ashhurst, Leo Corcilius, Richard J. Payne*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    6 Citations (Scopus)

    Abstract

    Mild strategies for the selective modification of peptides and proteins are in demand for applications in therapeutic peptide and protein discovery, and in the study of fundamental biomolecular processes. Herein, we describe the development of an electrochemical selenoetherification (e-SE) platform for the efficient site-selective functionalization of polypeptides. This methodology utilizes the unique reactivity of the 21st amino acid, selenocysteine, to effect formation of valuable bioconjugates through stable selenoether linkages under mild electrochemical conditions. The power of e-SE is highlighted through late-stage C-terminal modification of the FDA-approved cancer drug leuprolide and assembly of a library of anti-HER2 affibody conjugates bearing complex cargoes. Following assembly by e-SE, the utility of functionalized affibodies for in vitro imaging and targeting of HER2 positive breast and lung cancer cell lines is also demonstrated.

    Original languageEnglish
    Article numbere202313037
    JournalAngewandte Chemie - International Edition
    Volume62
    Issue number50
    DOIs
    Publication statusPublished - 11 Dec 2023

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