通过点击化学将配体与预制脂质体表面进行共轭。

Conjugation of ligands to the surface of preformed liposomes by click chemistry.

作者信息

Frisch Benoît, Hassane Fatouma Saïd, Schuber Francis

机构信息

Départment de Chimie Bioorganique, Faculté de Pharmacie, Institut Gilbert Lautriat, UMR 7175-LC1 CNRS-Université Louis Pasteur, Strasbourg-Illkirch, France.

出版信息

Methods Mol Biol. 2010;605:267-77. doi: 10.1007/978-1-60327-360-2_18.

Abstract

Click chemistry represents a new bioconjugation strategy that can be used to conveniently attach various ligands to the surface of preformed liposomes. This efficient and chemoselective reaction involves a Cu(I)-catalyzed azide-alkyne cycloaddition, which can be performed under mild experimental conditions in aqueous media. Here, we describe the application of a model click reaction to the conjugation, in a single step of unprotected alpha-1-thiomannosyl ligands, functionalized with an azide group to liposomes containing a terminal alkyne-functionalized lipid anchor. Excellent coupling yields were obtained in the presence of bathophenanthrolinedisulphonate, a water soluble copper-ion chelator, acting as a catalyst. No vesicle leakage was triggered by this conjugation reaction and the coupled mannose ligands were exposed at the surface of the liposomes. The major limitation of Cu(I)-catalyzed click reactions is that this conjugation is restricted to liposomes made of saturated (phospho)lipids. Efficient copper-free azide-alkyne click reactions are, however, being developed, which should alleviate this constraint in the future.

摘要

点击化学代表了一种新的生物共轭策略,可用于方便地将各种配体连接到预制脂质体的表面。这种高效且具有化学选择性的反应涉及铜(I)催化的叠氮化物-炔烃环加成反应,该反应可在水性介质中的温和实验条件下进行。在此,我们描述了一种模型点击反应在将用叠氮基团功能化的未保护α-1-硫代甘露糖基配体一步共轭到含有末端炔烃功能化脂质锚的脂质体中的应用。在水溶性铜离子螯合剂bathophenanthrolinedisulphonate作为催化剂存在的情况下,获得了优异的偶联产率。这种共轭反应未引发囊泡泄漏,并且偶联的甘露糖配体暴露在脂质体表面。铜(I)催化的点击反应的主要局限性在于这种共轭仅限于由饱和(磷酸)脂质制成的脂质体。然而,正在开发高效的无铜叠氮化物-炔烃点击反应,这有望在未来缓解这一限制。

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