Laboratory of Organic Chemistry, ETH Zurich, 8093, Zurich, Switzerland.
Nat Commun. 2020 Oct 26;11(1):5410. doi: 10.1038/s41467-020-19112-1.
Expanding protein design to include other molecular building blocks has the potential to increase structural complexity and practical utility. Nature often employs hybrid systems, such as clathrin-coated vesicles, lipid droplets, and lipoproteins, which combine biopolymers and lipids to transport a broader range of cargo molecules. To recapitulate the structure and function of such composite compartments, we devised a supramolecular strategy that enables porous protein cages to encapsulate poorly water-soluble small molecule cargo through templated formation of a hydrophobic surfactant-based core. These lipoprotein-like complexes protect their cargo from sequestration by serum proteins and enhance the cellular uptake of fluorescent probes and cytotoxic drugs. This design concept could be applied to other protein cages, surfactant mixtures, and cargo molecules to generate unique hybrid architectures and functional capabilities.
将其他分子构建块纳入蛋白质设计中具有增加结构复杂性和实际用途的潜力。自然界经常采用混合系统，如网格蛋白包被囊泡、脂滴和脂蛋白，它们将生物聚合物和脂质结合起来，以运输更广泛的货物分子。为了重现这种复合隔室的结构和功能，我们设计了一种超分子策略，使多孔蛋白质笼能够通过疏水表面活性剂基核的模板形成来封装水溶性差的小分子货物。这些类似脂蛋白的复合物可防止货物被血清蛋白隔离，并增强荧光探针和细胞毒性药物的细胞摄取。这种设计概念可以应用于其他蛋白质笼、表面活性剂混合物和货物分子，以产生独特的混合结构和功能能力。
