Synthesis of N-acetylglucosamine and N-acetylallosamine resorcinarene-based multivalent β-thio-glycoclusters: unexpected affinity of N-acetylallosamine ligands towards Wheat Germ Agglutinin.,Organic & Biomolecular Chemistry

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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.
Organic & Biomolecular Chemistry ( IF 2.9 ) Pub Date : 2020-08-21 , DOI: 10.1039/d0ob01498b
Alejandro E Cristófalo ₁ , Alejandro J Cagnoni , María Laura Uhrig

Affiliation

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.

中文翻译：

基于间苯二酚的 N-乙酰葡糖胺和 N-乙酰异糖胺多价 β-硫代糖簇的合成：N-乙酰异糖胺配体对麦芽凝集素的意外亲和力。

在此，我们报道了带有β- S -GlcNAc和β- S -AllNAc识别元件的基于杯[4]间苯二酚的多价配体的合成。利用 2,3-恶唑啉中间体，从 β-硫代炔基 GlcNAc 前体成功制备了可点击的 β- S -AllNAc 衍生物，该中间体很容易通过 2- N分子内置换位于 3 位的三氟甲磺酸酯基团形成-乙酸酯基团。通过这些炔基官能化衍生物与具有十一烷基链的八叠氮基-杯[4]间苯二肟大环的反应，获得了暴露出差向异构N-乙酰基己糖胺的两个八价糖簇。此外，还合成了相关的基于杯[4]间苯二酚的糖簇，其具有甲基而不是十一烷基链和β -S -GlcNAc残基。通过比浊法实验初步评估十一烷基功能化的 β- S -GlcNAc 八价衍生物与麦芽凝集素 (WGA) 的相互作用后，通过等温滴定量热法研究了三种合成的糖簇与 WGA 的相互作用。结果表明，由于十一烷基链的存在，在亲和力方面具有良好的效果。令人惊讶的是，β- S -AllNAc 八价化合物在所评估的糖簇中表现出最高的亲和力，这首次表明 WGA 与带有 β-AllNAc 的配体相互作用。 β-AllNAc 与 WGA 与 β-GlcNAc 的分子对接研究有助于理解导致这种意外亲和力的原子相互作用。

更新日期：2020-09-16

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