Co-Assembly of Liposomes, Dendrimersomes, and Polymersomes with Amphiphilic Janus Dendrimers Conjugated to Mono- and Tris-Nitrilotriacetic Acid (NTA, TrisNTA) Enhances Protein Recruitment
Co-Assembly of Liposomes, Dendrimersomes, and Polymersomes with Amphiphilic Janus Dendrimers Conjugated to Mono- and Tris-Nitrilotriacetic Acid (NTA, TrisNTA) Enhances Protein Recruitment
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DOI：
10.1016/j.giant.2021.100089
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发表时间：
2021-12
期刊：
影响因子：
7
通讯作者：
Qi Xiao;Naomi Rivera-Martinez;Calvin J. Raab;Jessica G. Bermudez;Matthew C. Good;M. Klein;V. Percec
中科院分区：
文献类型：
--
作者：
Qi Xiao;Naomi Rivera-Martinez;Calvin J. Raab;Jessica G. Bermudez;Matthew C. Good;M. Klein;V. Percec
金属螯合配体如次氮基三乙酸（NTA）与多组氨酸标记的（His标记的）蛋白质结合。在细胞生物学应用中，与NTA缀合的脂质广泛用于用蛋白质修饰脂质体的表面。当与脂质体中的磷脂和胆固醇共组装时，多价NTA配体如三次氮基三乙酸（TrisNTA）显示出比单价NTA更高的亲和力。然而，与NTA缀合的可用脂质的数量有限，并且只有少数是市售的。此外，它们的活性在储存期间或暴露于空气时会降低。在这里，我们报告了一个库的五个两亲性Janus树枝状大分子共轭NTA（JD-NTA）和三个TrisNTA（JD-TrisNTA）。JD-NTA和JD-TrisNTA在室温下在空气中均无限期稳定，初步结果表明，它们与磷脂和胆固醇共组装成脂质体，与Janus树枝状聚合物共组装成树枝状聚合物体，并与嵌段共聚物共组装成聚合物体。与脂质-NTA相比，与JD-NTA共组装的所得混合脂质体对His标记的荧光蛋白显示高达30倍的活性。与JD-TrisNTA共组装的杂合脂质体表现出对His标记的蛋白质甚至更高的结合亲和力，并且可以在杂合脂质体中比含有JD-NTA的那些低得多的配体浓度下起作用。这些初步结果证明了JD-NTA或JD-TrisNTA的模块化合成为生物重建和合成细胞生物学以及纳米医学提供高效新工具的能力。
Metal-chelating ligands such as nitrilotriacetic acid (NTA) bind to polyhistidine-tagged (His-tagged) proteins. Lipids conjugated to NTA are widely used to decorate the surface of liposomes with proteins in cell biology applications. Multivalent NTA ligands such as tris-nitrilotriacetic acid (TrisNTA) display higher affinities than the monovalent NTA when co-assembled with phospholipids and cholesterol in liposomes. However, there is a limited number of available lipids conjugated to NTA and only few are commercially available. Additionally, their activity diminishes during storage or upon exposure to air. Here we report a library of five amphiphilic Janus dendrimers conjugated to NTA (JD-NTA) and three to TrisNTA (JD-TrisNTA). Both JD-NTA and JD-TrisNTA are indefinitely stable at room temperature in air and preliminary results demonstrate that they co-assemble with phospholipids and cholesterol into liposomes, with Janus dendrimers into dendrimersomes, and with block copolymers into polymersomes. The resulting hybrid liposomes co-assembled with JD-NTA display up to thirty-fold higher activity towards His-tagged fluorescent proteins when compared to lipid-NTAs. Hybrid liposomes co-assembled with JD-TrisNTA exhibit even higher binding affinity to His-tagged proteins and can function at much lower ligand concentration in hybrid liposomes than those containing JD-NTA. These preliminary results demonstrate the power of modular synthesis of JD-NTA or JD-TrisNTA to provide highly efficient new tools for biological reconstitution and synthetic cell biology as well as for nanomedicine.