| Title: |
Bambus[4,6]urils as dual scaffolds for multivalent iminosugar presentation and ion transport: access to unprecedented glycosidase-directed anion caging agents |
| Authors: |
Lafosse, Marine; Liang, Yan; Schneider, Jérémy, P; Cartier, Elise; Bodlenner, Anne; Compain, Philippe; Heck, Marie-Pierre |
| Contributors: |
Service de Chimie Bio-Organique et de Marquage (SCBM); Médicaments et Technologies pour la Santé (MTS); Université Paris-Saclay-Institut des Sciences du Vivant Frédéric JOLIOT (JOLIOT); Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Institut des Sciences du Vivant Frédéric JOLIOT (JOLIOT); Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE); Laboratoire d'innovation moléculaire et applications (LIMA); Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut de Chimie - CNRS Chimie (INC-CNRS)-Centre National de la Recherche Scientifique (CNRS); the CEA (Commissariat à l’Energie Atomique); the International Centre for Frontier Research in Chemistry (icFRC); the Chinese Scholarship Council (CSC); the University of Strasbourg and the CNRS (LIMA-UMR 7042) |
| Source: |
ISSN: 1420-3049 ; Molecules ; https://cea.hal.science/cea-04361621 ; Molecules, 2022, 27 (15), pp.4772. ⟨10.3390/molecules27154772⟩ ; https://www.mdpi.com/1420-3049/27/15/4772. |
| Publisher Information: |
CCSD; MDPI |
| Publication Year: |
2022 |
| Subject Terms: |
bambusuril; multivalency; iminosugars; CuAAC; enzyme inhibition; DNJ; α-mannosidase; [CHIM]Chemical Sciences |
| Description: |
International audience ; Bambusurils, BU[4] and BU[6], were used for the first time as multivalent scaffolds to link glycosidases inhibitors derived from 1-deoxynojirimycin (DNJ). Two linear DNJ ligands having six or nine carbon alkyl azido linkers or a trivalent DNJ dendron were grafted onto octapropargylated BU[4] and dodecapropargylated BU[6] using copper-catalyzed cycloaddition (CuAAC) to yield corresponding neoglycobambus[4] and neoglycobambus[6]urils bearing 8 to 24 iminosugars. The inhibition potencies of neoglycoBU[4], neoglycoBU[6] and neoglycoBU[6] caging anions were evaluated against Jack Bean α-mannosidase and compared to monovalent DNJ derivatives. Strong affinity enhancements per inhibitory head were obtained for the clusters holding trivalent dendrons with inhibitory constants in the nanomolar range (K$_i$ = 24 nM for BU[4] with 24 DNJ units). Interestingly, the anion (bromide or iodide) encapsulated inside the cavity of BU[6] does not modify the inhibition potency of neoglycoBU[6], opening the way to water-soluble glycosidase-directed anion caging agents that may find applications in important fields such as bio(in)organic chemistry or oncology. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.3390/molecules27154772 |
| Availability: |
https://cea.hal.science/cea-04361621; https://cea.hal.science/cea-04361621v1/document; https://cea.hal.science/cea-04361621v1/file/molecules2022-27-04772.pdf; https://doi.org/10.3390/molecules27154772 |
| Rights: |
http://creativecommons.org/licenses/by-nc/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.CBBFADB6 |
| Database: |
BASE |