Fragment‐Based Drug Design Facilitated by Protein‐Templated Click Chemistry: Fragment Linking and Optimization of Inhibitors of the Aspartic Protease Endothiapepsin |
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Authors: | Dr Milon Mondal M Yagiz Unver Dr Asish Pal Matthijs Bakker Stephan P Berrier Prof Dr Anna K H Hirsch |
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Institution: | 1. Stratingh Institute for Chemistry, University of Groningen, Groningen, The Netherlands;2. Institute of Nano Science and Technology, Sector 64, Mohali, Punjab, India |
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Abstract: | There is an urgent need for the development of efficient methodologies that accelerate drug discovery. We demonstrate that the strategic combination of fragment linking/optimization and protein‐templated click chemistry is an efficient and powerful method that accelerates the hit‐identification process for the aspartic protease endothiapepsin. The best binder, which inhibits endothiapepsin with an IC50 value of 43 μm , represents the first example of triazole‐based inhibitors of endothiapepsin. Our strategy could find application on a whole range of drug targets. |
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Keywords: | click chemistry drug design enzymes inhibitors liquid chromatography |
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