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Iminosugar‐Cyclopeptoid Conjugates Raise Multivalent Effect in Glycosidase Inhibition at Unprecedented High Levels |
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| Authors: | Dr. Mathieu L. Lepage Jérémy P. Schneider Dr. Anne Bodlenner Alessandra Meli Prof. Francesco De Riccardis Dr. Marjorie Schmitt Prof. Céline Tarnus Dr. Nha‐Thi Nguyen‐Huynh Dr. Yannis‐Nicolas Francois Dr. Emmanuelle Leize‐Wagner Dr. Catherine Birck Alexandra Cousido‐Siah Dr. Alberto Podjarny Prof. Irene Izzo Prof. Philippe Compain |
| Affiliation: | 1. Laboratoire de Synthèse Organique et Molécules Bioactives Université de Strasbourg et CNRS (UMR 7509), Ecole Européenne de Chimie, Polymères et Matériaux, Strasbourg, France;2. Department of Chemistry and Biology, University of Salerno, Fisciano, Salerno, Italy;3. Université de Haute Alsace, Laboratoire de Chimie Organique et Bioorganique (EA4466), ENSCMu, Mulhouse Cedex, France;4. Laboratoire de Spectrométrie de Masse des Interactions et des Systèmes, UMR CNRS 7140, Université de Strasbourg, Strasbourg, France;5. Structural Biology Platform, CBI-IGBMC, Illkirch, France;6. Department of Integrative Biology, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS, INSERM, UdS, Illkirch CEDEX, France |
| Abstract: | A series of cyclopeptoid‐based iminosugar clusters has been evaluated to finely probe the ligand content‐dependent increase in α‐mannosidase inhibition. This study led to the largest binding enhancement ever reported for an enzyme inhibitor (up to 4700‐fold on a valency‐corrected basis), which represents a substantial advance over the multivalent glycosidase inhibitors previously reported. Electron microscopy imaging and analytical data support, for the best multivalent effects, the formation of a strong chelate complex in which two mannosidase molecules are cross‐linked by one inhibitor. |
| Keywords: | glycopeptides glycosidases iminosugars inhibitors multivalency |