Targeted liposomes: Convenient coupling of ligands to preformed vesicles using "click chemistry"
Targeted liposomes: Convenient coupling of ligands to preformed vesicles using "click chemistry"
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DOI：
10.1021/bc0503081
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发表时间：
2006-05-17
影响因子：
4.7
通讯作者：
Schuber, Francis
中科院分区：
文献类型：
--
作者：
Hassane, Fatouma Said;Frisch, Benoit;Schuber, Francis
基于“点击化学”的化学选择性偶联方法是将配体偶联到预先形成的脂质体表面的一种有效和方便的方法。它可以在温和的条件下在水性缓冲液中进行;使用水溶性Cu（I）螯合剂，如红菲咯啉二磺酸盐，对于在合理的反应时间内获得良好的产率是必不可少的。实现了模型反应，其中在单个步骤中，将携带用叠氮基官能化的间隔臂的未保护的α-D-甘露糖基衍生物缀合至呈现携带末端炔官能团的合成脂质的囊泡表面。当使用由饱和磷脂组成的脂质体时，在本工作中开发的反应条件不损害膜，如通过不存在截留的5，6-羧基荧光素的泄漏所测量的。此外，如通过使用伴刀豆球蛋白A的凝集实验所评估的，甘露糖残基在靶向囊泡的表面上是完全可接近的。
An efficient and convenient chemoselective conjugation method based on "click chemistry" was developed for coupling ligands to the surface of preformed liposomes. It can be performed under mild conditions in aqueous buffers; the use of a water soluble Cu(I) chelator, such as bathophenanthrolinedisulfonate, was essential to obtain good yields in reasonable reaction times. A model reaction was achieved in which, in a single step, an unprotected alpha-D-mannosyl derivative carrying a spacer arm functionalized with an azide group was conjugated to the surface of vesicles presenting a synthetic lipid carrying a terminal alkyne function. When liposomes composed of saturated phospholipids were used, the reaction conditions developed in the present work did not damage the membranes as measured by the absence of leakage of entrapped 5,6-carboxyfluorescein. Moreover, as assessed by agglutination experiments using concanavalin A, the mannose residues were perfectly accessible on the surface of the targeted vesicles.