An Advanced ‘clickECM’ That Can be Modified by the Inverse-Electron-Demand Diels-Alder Reaction |
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Authors: | Svenja Nellinger Mareike A Rapp Dr Alexander Southan Prof?Dr Valentin Wittmann Prof?Dr Petra J Kluger |
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Affiliation: | 1. Reutlingen Research Institute, Reutlingen University, School of Applied Chemistry, Alteburgstr. 150, 72762 Reutlingen, Germany;2. Department of Chemistry and Konstanz Research School Chemical Biology (KoRS-CB), University of Konstanz, Universitätsstr. 10, 78457 Konstanz, Germany;3. Institute of Interfacial Process Engineering and Plasma Technology, University of Stuttgart, Nobelstr. 12, 70569 Stuttgart, Germany |
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Abstract: | The extracellular matrix (ECM) represents the natural environment of cells in tissue and therefore is a promising biomaterial in a variety of applications. Depending on the purpose, it is necessary to equip the ECM with specific addressable functional groups for further modification with bioactive molecules, for controllable cross-linking and/or covalent binding to surfaces. Metabolic glycoengineering (MGE) enables the specific modification of the ECM with such functional groups without affecting the native structure of the ECM. In a previous approach (S. M. Ruff, S. Keller, D. E. Wieland, V. Wittmann, G. E. M. Tovar, M. Bach, P. J. Kluger, Acta Biomater. 2017 , 52, 159–170), we demonstrated the modification of an ECM with azido groups, which can be addressed by bioorthogonal copper-catalyzed azide-alkyne cycloaddition (CuAAC). Here, we demonstrate the modification of an ECM with dienophiles (terminal alkenes, cyclopropene), which can be addressed by an inverse-electron-demand Diels-Alder (IEDDA) reaction. This reaction is cell friendly as there are no cytotoxic catalysts needed. We show the equipment of the ECM with a bioactive molecule (enzyme) and prove that the functional groups do not influence cellular behavior. Thus, this new material has great potential for use as a biomaterial, which can be individually modified in a wide range of applications. |
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Keywords: | bioorthogonal chemistry carbohydrates extracellular matrix inverse-electron-demand Diels-Alder reaction metabolic engineering |
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