Cargando…

A flow platform for degradation-free CuAAC bioconjugation

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 br...

Descripción completa

Detalles Bibliográficos
Autores principales: Hatit, Marine Z. C., Reichenbach, Linus F., Tobin, John M., Vilela, Filipe, Burley, Glenn A., Watson, Allan J. B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6167327/
https://www.ncbi.nlm.nih.gov/pubmed/30275543
http://dx.doi.org/10.1038/s41467-018-06551-0
_version_ 1783360171703009280
author Hatit, Marine Z. C.
Reichenbach, Linus F.
Tobin, John M.
Vilela, Filipe
Burley, Glenn A.
Watson, Allan J. B.
author_facet Hatit, Marine Z. C.
Reichenbach, Linus F.
Tobin, John M.
Vilela, Filipe
Burley, Glenn A.
Watson, Allan J. B.
author_sort Hatit, Marine Z. C.
collection PubMed
description 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.
format Online
Article
Text
id pubmed-6167327
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-61673272018-10-03 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. Nat Commun Article 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. Nature Publishing Group UK 2018-10-01 /pmc/articles/PMC6167327/ /pubmed/30275543 http://dx.doi.org/10.1038/s41467-018-06551-0 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
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
title A flow platform for degradation-free CuAAC bioconjugation
title_full A flow platform for degradation-free CuAAC bioconjugation
title_fullStr A flow platform for degradation-free CuAAC bioconjugation
title_full_unstemmed A flow platform for degradation-free CuAAC bioconjugation
title_short A flow platform for degradation-free CuAAC bioconjugation
title_sort flow platform for degradation-free cuaac bioconjugation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6167327/
https://www.ncbi.nlm.nih.gov/pubmed/30275543
http://dx.doi.org/10.1038/s41467-018-06551-0
work_keys_str_mv AT hatitmarinezc aflowplatformfordegradationfreecuaacbioconjugation
AT reichenbachlinusf aflowplatformfordegradationfreecuaacbioconjugation
AT tobinjohnm aflowplatformfordegradationfreecuaacbioconjugation
AT vilelafilipe aflowplatformfordegradationfreecuaacbioconjugation
AT burleyglenna aflowplatformfordegradationfreecuaacbioconjugation
AT watsonallanjb aflowplatformfordegradationfreecuaacbioconjugation
AT hatitmarinezc flowplatformfordegradationfreecuaacbioconjugation
AT reichenbachlinusf flowplatformfordegradationfreecuaacbioconjugation
AT tobinjohnm flowplatformfordegradationfreecuaacbioconjugation
AT vilelafilipe flowplatformfordegradationfreecuaacbioconjugation
AT burleyglenna flowplatformfordegradationfreecuaacbioconjugation
AT watsonallanjb flowplatformfordegradationfreecuaacbioconjugation