Synthesis and Glycosidase Inhibition Properties of Calix[8]arene-Based Iminosugar Click Clusters
A set of 6- to 24-valent clusters was constructed with terminal deoxynojirimycin (DNJ) inhibitory heads through C6 or C9 linkers by way of Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reactions between mono- or trivalent azido-armed iminosugars and calix[8]arene scaffolds differing in their va...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-11-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/13/11/366 |
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| author | Jérémy P. Schneider Stefano Tommasone Paolo Della Sala Carmine Gaeta Carmen Talotta Céline Tarnus Placido Neri Anne Bodlenner Philippe Compain |
| author_facet | Jérémy P. Schneider Stefano Tommasone Paolo Della Sala Carmine Gaeta Carmen Talotta Céline Tarnus Placido Neri Anne Bodlenner Philippe Compain |
| author_sort | Jérémy P. Schneider |
| collection | DOAJ |
| description | A set of 6- to 24-valent clusters was constructed with terminal deoxynojirimycin (DNJ) inhibitory heads through C6 or C9 linkers by way of Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reactions between mono- or trivalent azido-armed iminosugars and calix[8]arene scaffolds differing in their valency and their rigidity but not in their size. The power of multivalency to upgrade the inhibition potency of the weak DNJ inhibitor (monovalent DNJ <i>K<sub>i</sub></i> being at 322 and 188 µM for C6 or C9 linkers, respectively) was evaluated on the model glycosidase Jack Bean α-mannosidase (JBα-man). Although for the clusters with the shorter C6 linker the rigidity of the scaffold was essential, these parameters had no influence for clusters with C9 chains: all of them showed rather good relative affinity enhancements per inhibitory epitopes between 70 and 160 highlighting the sound combination of the calix[8]arene core and the long alkyl arms. Preliminary docking studies were performed to get insights into the preferred binding modes. |
| first_indexed | 2024-03-10T15:04:58Z |
| format | Article |
| id | doaj.art-463ec6affc634d408ac87795bd8767ce |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T15:04:58Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-463ec6affc634d408ac87795bd8767ce2023-11-20T19:52:15ZengMDPI AGPharmaceuticals1424-82472020-11-01131136610.3390/ph13110366Synthesis and Glycosidase Inhibition Properties of Calix[8]arene-Based Iminosugar Click ClustersJérémy P. Schneider0Stefano Tommasone1Paolo Della Sala2Carmine Gaeta3Carmen Talotta4Céline Tarnus5Placido Neri6Anne Bodlenner7Philippe Compain8Laboratoire d’Innovation Moléculaire et Applications (LIMA), University of Strasbourg | University of Haute-Alsace | CNRS (UMR 7042), Equipe de Synthèse Organique et Molécules Bioactives (SYBIO), ECPM, 25 Rue Becquerel, 67000 Strasbourg, FranceLaboratory of Supramolecular Chemistry (SupraLab@UniSa), Dipartimento di Chimica e Biologia “A. Zambelli”, Università di Salerno, Via Giovanni Paolo II 132, I-84084 Fisciano, ItalyLaboratory of Supramolecular Chemistry (SupraLab@UniSa), Dipartimento di Chimica e Biologia “A. Zambelli”, Università di Salerno, Via Giovanni Paolo II 132, I-84084 Fisciano, ItalyLaboratory of Supramolecular Chemistry (SupraLab@UniSa), Dipartimento di Chimica e Biologia “A. Zambelli”, Università di Salerno, Via Giovanni Paolo II 132, I-84084 Fisciano, ItalyLaboratory of Supramolecular Chemistry (SupraLab@UniSa), Dipartimento di Chimica e Biologia “A. Zambelli”, Università di Salerno, Via Giovanni Paolo II 132, I-84084 Fisciano, ItalyLaboratoire Vigne Biotechnologies et Environnement EA-3991, University of Haute-Alsace, 33 rue de Herrlisheim, 68008 Colmar CEDEX, FranceLaboratory of Supramolecular Chemistry (SupraLab@UniSa), Dipartimento di Chimica e Biologia “A. Zambelli”, Università di Salerno, Via Giovanni Paolo II 132, I-84084 Fisciano, ItalyLaboratoire d’Innovation Moléculaire et Applications (LIMA), University of Strasbourg | University of Haute-Alsace | CNRS (UMR 7042), Equipe de Synthèse Organique et Molécules Bioactives (SYBIO), ECPM, 25 Rue Becquerel, 67000 Strasbourg, FranceLaboratoire d’Innovation Moléculaire et Applications (LIMA), University of Strasbourg | University of Haute-Alsace | CNRS (UMR 7042), Equipe de Synthèse Organique et Molécules Bioactives (SYBIO), ECPM, 25 Rue Becquerel, 67000 Strasbourg, FranceA set of 6- to 24-valent clusters was constructed with terminal deoxynojirimycin (DNJ) inhibitory heads through C6 or C9 linkers by way of Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reactions between mono- or trivalent azido-armed iminosugars and calix[8]arene scaffolds differing in their valency and their rigidity but not in their size. The power of multivalency to upgrade the inhibition potency of the weak DNJ inhibitor (monovalent DNJ <i>K<sub>i</sub></i> being at 322 and 188 µM for C6 or C9 linkers, respectively) was evaluated on the model glycosidase Jack Bean α-mannosidase (JBα-man). Although for the clusters with the shorter C6 linker the rigidity of the scaffold was essential, these parameters had no influence for clusters with C9 chains: all of them showed rather good relative affinity enhancements per inhibitory epitopes between 70 and 160 highlighting the sound combination of the calix[8]arene core and the long alkyl arms. Preliminary docking studies were performed to get insights into the preferred binding modes.https://www.mdpi.com/1424-8247/13/11/366multivalencyinhibitory multivalent effectCuAACcalix[8]areneα-mannosidase |
| spellingShingle | Jérémy P. Schneider Stefano Tommasone Paolo Della Sala Carmine Gaeta Carmen Talotta Céline Tarnus Placido Neri Anne Bodlenner Philippe Compain Synthesis and Glycosidase Inhibition Properties of Calix[8]arene-Based Iminosugar Click Clusters Pharmaceuticals multivalency inhibitory multivalent effect CuAAC calix[8]arene α-mannosidase |
| title | Synthesis and Glycosidase Inhibition Properties of Calix[8]arene-Based Iminosugar Click Clusters |
| title_full | Synthesis and Glycosidase Inhibition Properties of Calix[8]arene-Based Iminosugar Click Clusters |
| title_fullStr | Synthesis and Glycosidase Inhibition Properties of Calix[8]arene-Based Iminosugar Click Clusters |
| title_full_unstemmed | Synthesis and Glycosidase Inhibition Properties of Calix[8]arene-Based Iminosugar Click Clusters |
| title_short | Synthesis and Glycosidase Inhibition Properties of Calix[8]arene-Based Iminosugar Click Clusters |
| title_sort | synthesis and glycosidase inhibition properties of calix 8 arene based iminosugar click clusters |
| topic | multivalency inhibitory multivalent effect CuAAC calix[8]arene α-mannosidase |
| url | https://www.mdpi.com/1424-8247/13/11/366 |
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