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Modular Synthetic Approach to Carboranyl‒Biomolecules Conjugates

The development of novel, tumor-selective and boron-rich compounds as potential agents for use in boron neutron capture therapy (BNCT) represents a very important field in cancer treatment by radiation therapy. Here, we report the design and synthesis of two promising compounds that combine meta-car...

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Autores principales: Kellert, Martin, Friedrichs, Jan-Simon Jeshua, Ullrich, Nadine Anke, Feinhals, Alexander, Tepper, Jonas, Lönnecke, Peter, Hey-Hawkins, Evamarie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038343/
https://www.ncbi.nlm.nih.gov/pubmed/33916755
http://dx.doi.org/10.3390/molecules26072057
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author Kellert, Martin
Friedrichs, Jan-Simon Jeshua
Ullrich, Nadine Anke
Feinhals, Alexander
Tepper, Jonas
Lönnecke, Peter
Hey-Hawkins, Evamarie
author_facet Kellert, Martin
Friedrichs, Jan-Simon Jeshua
Ullrich, Nadine Anke
Feinhals, Alexander
Tepper, Jonas
Lönnecke, Peter
Hey-Hawkins, Evamarie
author_sort Kellert, Martin
collection PubMed
description The development of novel, tumor-selective and boron-rich compounds as potential agents for use in boron neutron capture therapy (BNCT) represents a very important field in cancer treatment by radiation therapy. Here, we report the design and synthesis of two promising compounds that combine meta-carborane, a water-soluble monosaccharide and a linking unit, namely glycine or ethylenediamine, for facile coupling with various tumor-selective biomolecules bearing a free amino or carboxylic acid group. In this work, coupling experiments with two selected biomolecules, a coumarin derivative and folic acid, were included. The task of every component in this approach was carefully chosen: the carborane moiety supplies ten boron atoms, which is a tenfold increase in boron content compared to the l-boronophenylalanine (l-BPA) presently used in BNCT; the sugar moiety compensates for the hydrophobic character of the carborane; the linking unit, depending on the chosen biomolecule, acts as the connection between the tumor-selective component and the boron-rich moiety; and the respective tumor-selective biomolecule provides the necessary selectivity. This approach makes it possible to develop a modular and feasible strategy for the synthesis of readily obtainable boron-rich agents with optimized properties for potential applications in BNCT.
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spelling pubmed-80383432021-04-12 Modular Synthetic Approach to Carboranyl‒Biomolecules Conjugates Kellert, Martin Friedrichs, Jan-Simon Jeshua Ullrich, Nadine Anke Feinhals, Alexander Tepper, Jonas Lönnecke, Peter Hey-Hawkins, Evamarie Molecules Article The development of novel, tumor-selective and boron-rich compounds as potential agents for use in boron neutron capture therapy (BNCT) represents a very important field in cancer treatment by radiation therapy. Here, we report the design and synthesis of two promising compounds that combine meta-carborane, a water-soluble monosaccharide and a linking unit, namely glycine or ethylenediamine, for facile coupling with various tumor-selective biomolecules bearing a free amino or carboxylic acid group. In this work, coupling experiments with two selected biomolecules, a coumarin derivative and folic acid, were included. The task of every component in this approach was carefully chosen: the carborane moiety supplies ten boron atoms, which is a tenfold increase in boron content compared to the l-boronophenylalanine (l-BPA) presently used in BNCT; the sugar moiety compensates for the hydrophobic character of the carborane; the linking unit, depending on the chosen biomolecule, acts as the connection between the tumor-selective component and the boron-rich moiety; and the respective tumor-selective biomolecule provides the necessary selectivity. This approach makes it possible to develop a modular and feasible strategy for the synthesis of readily obtainable boron-rich agents with optimized properties for potential applications in BNCT. MDPI 2021-04-03 /pmc/articles/PMC8038343/ /pubmed/33916755 http://dx.doi.org/10.3390/molecules26072057 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kellert, Martin
Friedrichs, Jan-Simon Jeshua
Ullrich, Nadine Anke
Feinhals, Alexander
Tepper, Jonas
Lönnecke, Peter
Hey-Hawkins, Evamarie
Modular Synthetic Approach to Carboranyl‒Biomolecules Conjugates
title Modular Synthetic Approach to Carboranyl‒Biomolecules Conjugates
title_full Modular Synthetic Approach to Carboranyl‒Biomolecules Conjugates
title_fullStr Modular Synthetic Approach to Carboranyl‒Biomolecules Conjugates
title_full_unstemmed Modular Synthetic Approach to Carboranyl‒Biomolecules Conjugates
title_short Modular Synthetic Approach to Carboranyl‒Biomolecules Conjugates
title_sort modular synthetic approach to carboranyl‒biomolecules conjugates
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038343/
https://www.ncbi.nlm.nih.gov/pubmed/33916755
http://dx.doi.org/10.3390/molecules26072057
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