Synthesis of Dodecavalent Fullerene-Based Glycoclusters and Evaluation of Their Binding Properties towards a Bacterial Lectin
Synthesis of Dodecavalent Fullerene-Based Glycoclusters and Evaluation of Their Binding Properties towards a Bacterial Lectin
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DOI：
10.1002/chem.201003258
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发表时间：
2011-03-01
影响因子：
4.3
通讯作者：
Vidal, Sebastien
中科院分区：
文献类型：
--
作者：
Cecioni, Samy;Oerthel, Vincent;Vidal, Sebastien
多价性在生物过程中起着重要作用，特别是在凝集素-碳水化合物相互作用中。凝集素的高亲和力配体的设计应该提供能够干扰这些生物过程并潜在地抑制细菌或病毒感染的分子。叠氮化物-炔“点击”化学被应用于十二价富勒烯基糖簇的合成。共轭可以有效地进行从炔或叠氮化物功能的任何合作伙伴（即六富勒烯加合物或糖苷）。PA-IL是来自机会致病菌铜绿假单胞菌的细菌凝集素，并且参与识别人体组织上的糖缀合物。作为PA-IL的配体和它们的潜在竞争与它的结合糖基化的表面得到的糖簇进行了评价。通过血凝抑制试验（HIA），酶联凝集素试验（ELLA）和表面等离子体共振（SPR）测量的亲和力显示出显着的“糖苷簇效应”，当将单价碳水化合物参考探针与十二价富勒烯基糖簇进行比较时，结合增加了12 000倍，尽管根据分析技术存在一些差异。
Multivalency is playing a major role in biological processes and particularly in lectin-carbohydrate interactions. The design of high-affinity ligands of lectins should provide molecules capable of interfering with these biological processes and potentially inhibit bacterial or viral infections. Azide-alkyne "click" chemistry was applied to the synthesis of dodecavalent fullerene-based glycoclusters. The conjugation could be efficiently performed from alkyne or azide functions on either partners (i.e. hexakis-fullerene adduct or glycoside). PA-IL is a bacterial lectin from the opportunistic pathogen Pseudomonas aeruginosa and is involved in the recognition of glycoconjugates on human tissues. The glycoclusters obtained were evaluated as ligands of PA-IL and for their potential for competing with its binding to glycosylated surfaces. The affinities measured by hemagglutination inhibition assay (HIA), enzyme-linked lectin assay (ELLA), and surface plasmon resonance (SPR) displayed a significant "glycoside cluster effect" with up to a 12 000-fold increase in binding when comparing a monovalent carbohydrate reference probe with a dodecavalent fullerene-based glycocluster, albeit with some differences depending on the analytical technique.