Departments of Chemistry & Biology, Indian Institute of Science Education and Research (IISER), Pune, 411 008, India.
Tata Institute of Fundamental Research Hyderabad (TIFR Hyd), Hyderabad, 500019, India.
Chembiochem. 2020 Feb 3;21(3):408-416. doi: 10.1002/cbic.201900341. Epub 2019 Oct 30.
The custom design of protein-dendron amphiphilic macromolecules is at the forefront of macromolecular engineering. Macromolecules with this architecture are very interesting because of their ability to self-assemble into various biomimetic nanoscopic structures. However, to date, there are no reports on this concept due to technical challenges associated with the chemical synthesis. Towards that end, herein, a new chemical methodology for the modular synthesis of a suite of monodisperse, facially amphiphilic, protein-dendron bioconjugates is reported. Benzyl ether dendrons of different generations (G1-G4) are coupled to monodisperse cetyl ethylene glycol to form macromolecular amphiphilic activity-based probes (AABPs) with a single protein reactive functionality. Micelle-assisted protein labeling technology is utilized for site-specific conjugation of macromolecular AABPs to globular proteins to make monodisperse, facially amphiphilic, protein-dendron bioconjugates. These biohybrid conjugates have the ability to self-assemble into supramolecular protein nanoassemblies. Self-assembly is primarily mediated by strong hydrophobic interactions of the benzyl ether dendron domain. The size, surface charge, and oligomeric state of protein nanoassemblies could be systematically tuned by choosing an appropriate dendron or protein of interest. This chemical method discloses a new way to custom-make monodisperse, facially amphiphilic, protein-dendron bioconjugates.
蛋白质-树枝状两亲大分子的定制设计处于高分子工程的前沿。具有这种结构的大分子非常有趣，因为它们能够自组装成各种仿生纳米结构。然而，由于与化学合成相关的技术挑战，迄今为止，尚无关于该概念的报道。为此，本文报道了一种用于合成一系列单分散、双面两亲性、蛋白质-树枝状生物缀合物的模块化新化学方法。不同代（G1-G4）的苄醚树枝与单分散十六烷乙二醇偶联，形成具有单个蛋白质反应性官能团的两亲性基于活性的大分子探针（AABP）。利用胶束辅助蛋白质标记技术，将大分子 AABP 定点连接到球状蛋白质上，得到单分散、双面两亲性的蛋白质-树枝状生物缀合物。这些生物杂化物能够自组装成超分子蛋白质纳米组装体。自组装主要由苄醚树枝状结构域的强疏水性相互作用介导。通过选择合适的树枝或感兴趣的蛋白质，可以系统地调节蛋白质纳米组装体的大小、表面电荷和聚合态。这种化学方法揭示了一种定制单分散、双面两亲性、蛋白质-树枝状生物缀合物的新方法。
