A flow platform for degradation-free CuAAC bioconjugation

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Hatit, Marine Z. C. and Reichenbach, Linus F. and Tobin, John M. and Vilela, Filipe and Burley, Glenn A. and Watson, Allan J. B. (2018) A flow platform for degradation-free CuAAC bioconjugation. Nature Communications, 9. 4021. ISSN 2041-1723 (https://doi.org/10.1038/s41467-018-06551-0)

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Abstract

The Cu-catalyzed azide-alkyne cycloaddition (CuAAC) reaction is a cornerstone method for the ligation of biomolecules. However, undesired Cu-mediated oxidation and Cu-contamination in bioconjugates limits biomedical utility. Here, we report a generic CuAAC flow platform for the rapid, robust, and broad-spectrum formation of discrete triazole bioconjugates. This process leverages an engineering problem to chemical advantage: solvent-mediated Cu pipe erosion generates ppm levels of Cu in situ under laminar flow conditions. This is sufficient to catalyze the CuAAC reaction of small molecule alkynes and azides, fluorophores, marketed drug molecules, peptides, DNA, and therapeutic oligonucleotides. This flow approach, not replicated in batch, operates at ambient temperature and pressure, requires short residence times, avoids oxidation of sensitive functional groups, and produces products with very low ppm Cu contamination.

ORCID iDs

Hatit, Marine Z. C. ORCID logoORCID: https://orcid.org/0000-0002-5713-6596, Reichenbach, Linus F. ORCID logoORCID: https://orcid.org/0000-0002-9977-0659, Tobin, John M., Vilela, Filipe, Burley, Glenn A. and Watson, Allan J. B.;
  • Item type:Article
    ID code:65360
    Dates:
    Date
    Event
    1 October 2018
    Published
    4 September 2018
    Accepted
    Notes:Highlighted on October 2017's Nature Communications website as an important article.
    Subjects:Science > Chemistry
    Department:Faculty of Science > Pure and Applied Chemistry
    Depositing user: Pure Administrator
    Date deposited:05 Sep 2018 10:39
    Last modified:17 Dec 2024 17:02
    Related URLs:
    URI:https://strathprints.strath.ac.uk/id/eprint/65360
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