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Heterobifunctional Dyes: Highly Fluorescent Linkers Based on Cyanine Dyes

Herein, we present a new synthetic route to cyanine‐based heterobifunctional dyes and their application as fluorescent linkers between polymers and biomolecules. The synthesized compounds, designed in the visible spectral range, are equipped with two different reactive groups for highly selective co...

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Autores principales: Wycisk, Virginia, Achazi, Katharina, Hirsch, Ole, Kuehne, Christian, Dernedde, Jens, Haag, Rainer, Licha, Kai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5474662/
https://www.ncbi.nlm.nih.gov/pubmed/28638777
http://dx.doi.org/10.1002/open.201700013
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author Wycisk, Virginia
Achazi, Katharina
Hirsch, Ole
Kuehne, Christian
Dernedde, Jens
Haag, Rainer
Licha, Kai
author_facet Wycisk, Virginia
Achazi, Katharina
Hirsch, Ole
Kuehne, Christian
Dernedde, Jens
Haag, Rainer
Licha, Kai
author_sort Wycisk, Virginia
collection PubMed
description Herein, we present a new synthetic route to cyanine‐based heterobifunctional dyes and their application as fluorescent linkers between polymers and biomolecules. The synthesized compounds, designed in the visible spectral range, are equipped with two different reactive groups for highly selective conjugation under physiological conditions. By applying indolenine precursors with functionalized benzenes, we achieved water‐soluble asymmetric cyanine dyes bearing maleimido and N‐hydroxysuccinimidyl functionalities in a three‐step synthesis. Spectroscopic characterization revealed good molar absorption coefficients and moderate fluorescence quantum yields. Further reaction with polyethylene glycol yielded dye–polymer conjugates that were subsequently coupled to the antibody cetuximab, often applied in cancer therapy. Successful coupling was confirmed by mass shifts detected by gel electrophoresis. Receptor‐binding studies and live‐cell imaging revealed that labeling did not alter the biological function. In sum, we provided a successful synthetic pathway to rigid heterobifunctional cyanine dyes that are applicable as fluorescent linkers, for example, for connecting antibodies with macromolecules. Our approach contributes to the field of bioconjugation chemistry, such as antibody–drug conjugates by combining diagnostic and therapeutic approaches.
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spelling pubmed-54746622017-06-21 Heterobifunctional Dyes: Highly Fluorescent Linkers Based on Cyanine Dyes Wycisk, Virginia Achazi, Katharina Hirsch, Ole Kuehne, Christian Dernedde, Jens Haag, Rainer Licha, Kai ChemistryOpen Full Papers Herein, we present a new synthetic route to cyanine‐based heterobifunctional dyes and their application as fluorescent linkers between polymers and biomolecules. The synthesized compounds, designed in the visible spectral range, are equipped with two different reactive groups for highly selective conjugation under physiological conditions. By applying indolenine precursors with functionalized benzenes, we achieved water‐soluble asymmetric cyanine dyes bearing maleimido and N‐hydroxysuccinimidyl functionalities in a three‐step synthesis. Spectroscopic characterization revealed good molar absorption coefficients and moderate fluorescence quantum yields. Further reaction with polyethylene glycol yielded dye–polymer conjugates that were subsequently coupled to the antibody cetuximab, often applied in cancer therapy. Successful coupling was confirmed by mass shifts detected by gel electrophoresis. Receptor‐binding studies and live‐cell imaging revealed that labeling did not alter the biological function. In sum, we provided a successful synthetic pathway to rigid heterobifunctional cyanine dyes that are applicable as fluorescent linkers, for example, for connecting antibodies with macromolecules. Our approach contributes to the field of bioconjugation chemistry, such as antibody–drug conjugates by combining diagnostic and therapeutic approaches. John Wiley and Sons Inc. 2017-04-13 /pmc/articles/PMC5474662/ /pubmed/28638777 http://dx.doi.org/10.1002/open.201700013 Text en © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Full Papers
Wycisk, Virginia
Achazi, Katharina
Hirsch, Ole
Kuehne, Christian
Dernedde, Jens
Haag, Rainer
Licha, Kai
Heterobifunctional Dyes: Highly Fluorescent Linkers Based on Cyanine Dyes
title Heterobifunctional Dyes: Highly Fluorescent Linkers Based on Cyanine Dyes
title_full Heterobifunctional Dyes: Highly Fluorescent Linkers Based on Cyanine Dyes
title_fullStr Heterobifunctional Dyes: Highly Fluorescent Linkers Based on Cyanine Dyes
title_full_unstemmed Heterobifunctional Dyes: Highly Fluorescent Linkers Based on Cyanine Dyes
title_short Heterobifunctional Dyes: Highly Fluorescent Linkers Based on Cyanine Dyes
title_sort heterobifunctional dyes: highly fluorescent linkers based on cyanine dyes
topic Full Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5474662/
https://www.ncbi.nlm.nih.gov/pubmed/28638777
http://dx.doi.org/10.1002/open.201700013
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