Rim-differentiation vs. mixture of constitutional isomers: A binding study between pillar[5]arene-based glycoclusters and lectins from pathogenic bacteria  

作　　者：Zhiping Liu Fanny Demontrond Anne Imberty Andrew C.-H.Sue Sébastien Vidal Hongxia Zhao 

机构地区：[1]Tianjin Key Lab for Modern Drug Delivery and High-Efficiency,School of Pharmaceutical Science and Technology,Tianjin University,Tianjin 300072,China [2]Institut de Chimie et Biochimie Moléculaires et Supramoléculaires,Laboratoire de Chimie Organique 2-Glycochimie,UMR 5246,CNRS,UniversitéClaude Bernard Lyon 1,Universitéde Lyon,Villeurbanne 69622,France [3]CNRS,Univ.Grenoble Alpes,CERMAV,Grenoble 38000,France [4]College of Chemistry and Chemical Engineering,Xiamen University,Xiamen 361005,China [5]CNRS,Institut de Chimie des Substances Naturelles,UniversitéParis-Saclay,UPR 2301,Gif-sur-Yvette 91198,France

出　　处：《Chinese Chemical Letters》2023年第2期214-218,共5页中国化学快报（英文版）

基　　金：Financial supports from the National Natural Science Foundation of China (No. 21801184);the Tianjin Municipal Applied Basic and Key Research Scheme of China (No. 18JCQNJC06400);Xiamen University, Starry Night Science Fund of Zhejiang University Shanghai Institute for Advanced Study (No. SN-ZJU-SIAS-006);Université de Lyon, the French Agence Nationale de la Recherche (Dyna Sweet, ANR-08-BLAN-0305);Glyco@Alps (ANR-15-IDEX-02);Labex Arcane/CBH-EUR-GS (ANR-17-EURE-0003) are gratefully acknowledged。

摘　　要：Macrocycle-based glycoclusters, on account of their promising anti-adhesive properties against bacteria,are potential therapeutic alternatives to classic antibiotics through the much less explored anti-adhesive strategy. In this study, a series of constitutionally-pure pentavalent glycoclusters was prepared by conjugating assorted azido-carbohydrates onto a penta-propargyl rim-differentiated pillar[5]arene(RD-P[5])scaffold through Cu(I)-catalyzed azide–alkyne cycloaddition “click” reactions. Their binding towards therapeutically relevant bacterial lectins, such as Lec A and Lec B from Pseudomonas aeruginosa and concanavalin A(Con A), were evaluated subsequently by isothermal titration calorimetric studies. Most of these isomerfree RD-P[5] pentavalent glycoclusters, except the fucosylated ones, display good affinities to lectins.Nonetheless, the dissociation constants observed are similar to those displayed by an analogous pentavalent glycocluster consisting of four P[5] constitutional isomers, in which the RD-P[5] component merely accounts for 7% in the mixture. Our results revealed that high constitutional purity is not essential for achieving effective multivalent interactions between P[5]-based glycoclusters and lectins, presumably as a result of the conformationally labile nature of the P[5] scaffold. This information provides valuable design principles for low-cost and facile syntheses of glycosylated P[5]s for biomedical applications.

关 键 词：Glycocluster LECTIN Pillararene MULTIVALENCY Constitutional purity 

分 类 号：R914[医药卫生—药物化学]