Selective Disruption of Survivin's Protein-Protein Interactions: A Supramolecular Approach Based on Guanidiniocarbonylpyrrole |
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| Authors: | Dennis Aschmann Dr. Cecilia Vallet Dr. Sunil K. Tripathi Dr. Yasser B. Ruiz-Blanco Max Brabender Prof. Dr. Carsten Schmuck Prof. Dr. Elsa Sanchez-Garcia Prof. Dr. Shirley K. Knauer Prof.Dr. Michael Giese |
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| Affiliation: | 1. Department of Organic Chemistry, University of Duisburg-Essen, Universitätsstr. 7, 45141 Essen, Germany;2. Department of Molecular Biology II, University of Duisburg-Essen, Universitätsstr. 5, 45141 Essen, Germany;3. Computational Biochemistry, University of Duisburg-Essen, Universitätsstr. 2, 45117 Essen, Germany;4. Department of Organic Chemistry, University of Duisburg-Essen, Universitätsstr. 7, 45141 Essen, Germany Deceased August 2019. |
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| Abstract: | Targeting specific protein binding sites to interfere with protein-protein interactions (PPIs) is crucial for the rational modulation of biologically relevant processes. Survivin, which is highly overexpressed in most cancer cells and considered to be a key player of carcinogenesis, features two functionally relevant binding sites. Here, we demonstrate selective disruption of the Survivin/Histone H3 or the Survivin/Crm1 interaction using a supramolecular approach. By rational design we identified two structurally related ligands ( LNES and LHIS ), capable of selectively inhibiting these PPIs, leading to a reduction in cancer cell proliferation. |
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| Keywords: | cancer CL-FEP molecular recognition supramolecular chemistry survivin |
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