Institut des Biomolécules Max Mousseron UMR 5247 UM2-UM1-CNRS-ENSCM 8 rue de l'Ecole Normale, Montpellier cedex 5 34296, France.
Molecules. 2014 Jan 17;19(1):1120-49. doi: 10.3390/molecules19011120.
Herein, the preparation of neoglycoconjugates bearing mannose-6-phosphate analogues is described by: (a) synthesis of a cyclic sulfate precursor to access the carbohydrate head-group by nucleophilic displacement with an appropriate nucleophile; (b) introduction of spacers on the mannose-6-phosphate analogues via Huisgen's cycloaddition, the Julia reaction, or the thiol-ene reaction under ultrasound activation. With the resulting compounds in hand, gold nanoparticles could be functionalized with various carbohydrate derivatives (glycoconjugates) and then tested for angiogenic activity. It was observed that the length and flexibility of the spacer separating the sugar analogue from the nanoparticle have little influence on the biological response. One particular nanoparticle system substantially inhibits blood vessel growth in contrast to activation by the corresponding monomeric glycoconjugate, thereby demonstrating the importance of multivalency in angiogenic activity.
本文描述了通过以下方法制备带有甘露糖-6-磷酸类似物的糖基缀合物：（a）通过亲核取代反应用适当的亲核试剂合成环状硫酸盐前体，以获得碳水化合物的头基团；（b）通过点击化学、Julia 反应或超声激活下的硫醇-烯反应，在甘露糖-6-磷酸类似物上引入间隔基。得到的化合物可用于功能化各种糖衍生物（糖缀合物），然后测试其血管生成活性。结果表明，将糖类似物与纳米颗粒分离的间隔基的长度和灵活性对生物反应的影响很小。与相应的单体糖缀合物的激活相比，一种特殊的纳米颗粒系统显著抑制血管生长，从而证明了在血管生成活性中多价性的重要性。
