Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto 615-8510, Japan.
Bioconjug Chem. 2020 May 20;31(5):1259-1267. doi: 10.1021/acs.bioconjchem.0c00133. Epub 2020 Apr 26.
Molecular chaperones play critical roles in biological functions. They are closely involved in the maintenance of cell homeostasis, proper folding of proteins and nucleic acids, and inhibition of irreversible aggregation in denatured proteins. In addition to protein production, molecular chaperone function is widely recognized as important for peptide and protein drug delivery systems. Therefore, much effort has been made in recent decades to develop chaperone-mimetic molecules that have similar structures and biological functions to natural chaperones. These artificial molecular chaperone systems have been demonstrated to facilitate proper protein and nucleic acid folding, in addition to the formation of higher-order structures of synthetic molecules. Furthermore, the functions of these artificial systems show promising clinical applications in drug delivery and biomolecule detection. This topical review focuses on recent advances in the design, construction, characterization, and potential applications of different artificial molecular systems with distinct functional roles, such as the folding of water-soluble and membrane proteins, nucleic acids, and the self-assembly of synthetic molecules. Strategies used in the construction of some artificial molecule chaperone systems for proteins (such as pairs of amphiphilic molecules or self-assembled nanogels) and their applications as biomaterials are described. Specific examples from each design strategy are also highlighted to demonstrate the mechanisms, challenges, and limitations of the different artificial molecular systems. By highlighting the many new developments that have expanded the applications of the artificial chaperones beyond protein folding, this review aims to stimulate further studies on their design and applications.
分子伴侣在生物功能中起着至关重要的作用。它们密切参与细胞内环境的维持、蛋白质和核酸的正确折叠以及变性蛋白质不可逆聚集的抑制。除了蛋白质生产，分子伴侣的功能也被广泛认为对肽和蛋白质药物传递系统很重要。因此，近几十年来，人们做出了很多努力来开发具有与天然分子伴侣相似结构和生物学功能的伴侣模拟分子。这些人工分子伴侣系统已被证明可以促进蛋白质和核酸的正确折叠，以及合成分子的高级结构的形成。此外，这些人工系统的功能在药物传递和生物分子检测方面显示出有希望的临床应用。本专题综述重点介绍了不同人工分子系统的设计、构建、表征和潜在应用的最新进展，这些系统具有不同的功能作用，如水溶性和膜蛋白、核酸的折叠以及合成分子的自组装。还描述了一些用于蛋白质的人工分子伴侣系统（如两亲性分子对或自组装纳米凝胶）的构建策略及其作为生物材料的应用。还突出了每个设计策略的具体示例，以展示不同人工分子系统的机制、挑战和局限性。通过突出许多新的发展，这些发展将人工伴侣的应用扩展到了蛋白质折叠之外，本综述旨在激发对其设计和应用的进一步研究。
