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Issue 35, 2020
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Synthesis of N-acetylglucosamine and N-acetylallosamine resorcinarene-based multivalent β-thio-glycoclusters: unexpected affinity of N-acetylallosamine ligands towards Wheat Germ Agglutinin

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Abstract

Herein, we report the synthesis of calix[4]resorcinarene-based multivalent ligands bearing β-S-GlcNAc and β-S-AllNAc recognition elements. A clickable β-S-AllNAc derivative was successfully prepared from a β-thioalkynyl GlcNAc precursor, making use of a 2,3-oxazoline intermediate, easily formed by intramolecular displacement of a triflate group located at the 3-position by the 2-N-acetate group. By reaction of these alkynyl-functionalized derivatives with an octaazido-calix[4]resorcinarene macrocycle having undecyl chains, two octavalent glycoclusters exposing the epimeric N-acetylhexosamines were obtained. In addition, a related calix[4]resorcinarene-based glycocluster having methyl groups instead of undecyl chains and β-S-GlcNAc residues was also synthesized. After an initial evaluation of the interaction of the undecyl-functionalized β-S-GlcNAc octavalent derivative with Wheat Germ Agglutinin (WGA) by a turbidimetry experiment, the interaction of the three synthesized glycoclusters towards WGA was studied by Isothermal Titration Calorimetry. The results showed a favorable effect due to the presence of the undecyl chains in terms of affinity. Surprisingly, the β-S-AllNAc octavalent compound showed the highest affinity among the evaluated glycoclusters, showing for the first time that WGA interacts with β-AllNAc-bearing ligands. Molecular docking studies of β-AllNAc with WGA in comparison with β-GlcNAc contributed to the understanding of the atomic interactions responsible for this unexpected affinity.

Graphical abstract: Synthesis of N-acetylglucosamine and N-acetylallosamine resorcinarene-based multivalent β-thio-glycoclusters: unexpected affinity of N-acetylallosamine ligands towards Wheat Germ Agglutinin

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Supplementary files

Article information


Submitted
20 Jul 2020
Accepted
21 Aug 2020
First published
21 Aug 2020

Org. Biomol. Chem., 2020,18, 6853-6865
Article type
Paper

Synthesis of N-acetylglucosamine and N-acetylallosamine resorcinarene-based multivalent β-thio-glycoclusters: unexpected affinity of N-acetylallosamine ligands towards Wheat Germ Agglutinin

A. E. Cristófalo, A. J. Cagnoni and M. L. Uhrig, Org. Biomol. Chem., 2020, 18, 6853
DOI: 10.1039/D0OB01498B

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