Multivalent display of proteins on viral nanoparticles using molecular recognition and chemical ligation strategies.
Multivalent display of proteins on viral nanoparticles using molecular recognition and chemical ligation strategies.
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DOI：
10.1021/bm200369e
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发表时间：
2011-06-13
影响因子：
6.2
通讯作者：
Schneemann A
中科院分区：
文献类型：
--
作者：
Venter PA;Dirksen A;Thomas D;Manchester M;Dawson PE;Schneemann A
异源蛋白质在病毒纳米颗粒上的多价展示形成了纳米技术中许多应用的基础，包括疫苗开发、靶向治疗递送和组织特异性生物成像。在许多情况下，蛋白质的精确放置是超分子组装体的最佳功能所必需的，但是蛋白质与病毒支架的定向和位点特异性偶联仍然是一个重大的技术挑战。我们已经开发了两种策略，允许使用共价和非共价原理控制各种蛋白质在病毒颗粒上的附着。在一种策略中，炭疽保护性抗原的结构域4与其受体之间的相互作用用于在病毒样颗粒上展示靶蛋白的多个拷贝。另一种方法是利用表达蛋白的连接和苯胺催化的肟化反应来共价展示模型蛋白。特别是后一种策略，产生了纳米颗粒，诱导了对偶联蛋白的有效免疫反应，这表明在疫苗开发中有潜在的应用。
Multivalent display of heterologous proteins on viral nanoparticles forms a basis for numerous applications in nanotechnology, including vaccine development, targeted therapeutic delivery and tissue-specific bio-imaging. In many instances, precise placement of proteins is required for optimal functioning of the supramolecular assemblies, but orientation- and site-specific coupling of proteins to viral scaffolds remains a significant technical challenge. We have developed two strategies that allow for controlled attachment of a variety of proteins on viral particles using covalent and noncovalent principles. In one strategy, an interaction between domain 4 of anthrax protective antigen and its receptor was used to display multiple copies of a target protein on virus-like particles. In the other, expressed protein ligation and aniline-catalyzed oximation was used to covalently display a model protein. The latter strategy, in particular, yielded nanoparticles that induced potent immune responses to the coupled protein, suggesting potential applications in vaccine development.