Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095, USA.
Department of Bioengineering, University of California, Los Angeles, California 90095, USA.
Nat Chem. 2017 Apr;9(4):333-340. doi: 10.1038/nchem.2686. Epub 2016 Dec 19.
The majority of biomolecules are intrinsically atomically precise, an important characteristic that enables rational engineering of their recognition and binding properties. However, imparting a similar precision to hybrid nanoparticles has been challenging because of the inherent limitations of existing chemical methods and building blocks. Here we report a new approach to form atomically precise and highly tunable hybrid nanomolecules with well-defined three-dimensionality. Perfunctionalization of atomically precise clusters with pentafluoroaryl-terminated linkers produces size-tunable rigid cluster nanomolecules. These species are amenable to facile modification with a variety of thiol-containing molecules and macromolecules. Assembly proceeds at room temperature within hours under mild conditions, and the resulting nanomolecules exhibit high stabilities because of their full covalency. We further demonstrate how these nanomolecules grafted with saccharides can exhibit dramatically improved binding affinity towards a protein. Ultimately, the developed strategy allows the rapid generation of precise molecular assemblies to investigate multivalent interactions.
大多数生物分子在原子水平上是精确的，这一重要特性使其能够对其识别和结合特性进行合理的工程设计。然而，由于现有化学方法和构建块的固有局限性，赋予混合纳米粒子类似的精度一直具有挑战性。在这里，我们报告了一种新方法，可形成具有明确定三维结构的原子精确且高度可调的混合纳米分子。用五氟芳基末端连接物对原子精确的团簇进行全功能化，可得到尺寸可调的刚性团簇纳米分子。这些物质易于用各种含硫醇的分子和大分子进行修饰。在温和的条件下，室温下在数小时内即可进行组装，并且由于其完全的共价键，所得纳米分子表现出很高的稳定性。我们进一步证明了接枝有糖的这些纳米分子如何显著提高对蛋白质的结合亲和力。最终，所开发的策略允许快速生成精确的分子组装，以研究多价相互作用。
