Olson Arthur J, Hu Yunfeng H E, Keinan Ehud
Department of Molecular Biology and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Proc Natl Acad Sci U S A. 2007 Dec 26;104(52):20731-6. doi: 10.1073/pnas.0709489104. Epub 2007 Dec 18.
Stable structures of icosahedral symmetry can serve numerous functional roles, including chemical microencapsulation and delivery of drugs and biomolecules, epitope presentation to allow for an efficient immunization process, synthesis of nanoparticles of uniform size, observation of encapsulated reactive intermediates, formation of structural elements for supramolecular constructs, and molecular computing. By examining physical models of spherical virus assembly we have arrived at a general synthetic strategy for producing chemical capsids at size scales between fullerenes and spherical viruses. Such capsids can be formed by self-assembly from a class of molecules developed from a symmetric pentagonal core. By designing chemical complementarity into the five interface edges of the molecule, we can produce self-assembling stable structures of icosahedral symmetry. We considered three different binding mechanisms: hydrogen bonding, metal binding, and formation of disulfide bonds. These structures can be designed to assemble and disassemble under controlled environmental conditions. We have conducted molecular dynamics simulation on a class of corannulene-based molecules to demonstrate the characteristics of self-assembly and to aid in the design of the molecular subunits. The edge complementarities can be of diverse structure, and they need not reflect the fivefold symmetry of the molecular core. Thus, self-assembling capsids formed from coded subunits can serve as addressable nanocontainers or custom-made structural elements.
二十面体对称的稳定结构可发挥多种功能作用，包括化学微囊化以及药物和生物分子的递送、表位呈递以实现高效免疫过程、合成尺寸均匀的纳米颗粒、观察被封装的反应中间体、形成超分子构建体的结构元件以及分子计算。通过研究球形病毒组装的物理模型，我们得出了一种通用的合成策略，用于在富勒烯和球形病毒之间的尺寸尺度上制备化学衣壳。此类衣壳可通过一类由对称五角形核心衍生而来的分子自组装形成。通过在分子的五个界面边缘设计化学互补性，我们能够制备出具有二十面体对称的自组装稳定结构。我们考虑了三种不同的结合机制：氢键、金属结合以及二硫键的形成。这些结构可设计成在可控环境条件下进行组装和拆卸。我们对一类基于碗烯的分子进行了分子动力学模拟，以展示自组装的特性并辅助分子亚基的设计。边缘互补性可以具有多样的结构，且不必反映分子核心的五重对称性。因此，由编码亚基形成的自组装衣壳可作为可寻址的纳米容器或定制的结构元件。
