A flow platform for degradation-free CuAAC bioconjugation

Marine Z. C. Hatit, Linus F. Reichenbach, John M. Tobin, Filipe Vilela, Glenn A. Burley, Allan J. B. Watson

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.
LanguageEnglish
Article number4021
Number of pages7
JournalNature Communications
Volume9
DOIs
Publication statusPublished - 1 Oct 2018

Fingerprint

Alkynes
Azides
Cycloaddition
Cycloaddition Reaction
cycloaddition
alkynes
platforms
degradation
Degradation
contamination
Contamination
Oxidation
oxidation
Molecules
Triazoles
Fluorophores
oligonucleotides
Biomolecules
laminar flow
Laminar flow

Keywords

  • CuAAC flow platform
  • Cu-catalyzed azide-alkyne cycloaddition (CuAAC)
  • contamination

Cite this

Hatit, Marine Z. C. ; Reichenbach, Linus F. ; Tobin, John M. ; Vilela, Filipe ; Burley, Glenn A. ; Watson, Allan J. B. / A flow platform for degradation-free CuAAC bioconjugation. In: Nature Communications. 2018 ; Vol. 9.
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A flow platform for degradation-free CuAAC bioconjugation. / Hatit, Marine Z. C.; Reichenbach, Linus F.; Tobin, John M.; Vilela, Filipe; Burley, Glenn A.; Watson, Allan J. B.

In: Nature Communications, Vol. 9, 4021, 01.10.2018.

Research output: Contribution to journalArticle

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AU - Hatit, Marine Z. C.

AU - Reichenbach, Linus F.

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AU - Watson, Allan J. B.

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