Monkovic Julia M, Gibson Halle, Sun Jonathan W, Montclare Jin Kim
Department of Chemical and Biomolecular Engineering, NYU Tandon School of Engineering, Brooklyn, NY 11201, USA.
Department of Chemistry, New York University, New York, NY 10003, USA.
Pharmaceuticals (Basel). 2022 Sep 28;15(10):1201. doi: 10.3390/ph15101201.
Fluorination represents one of the most powerful modern design strategies to impart biomacromolecules with unique functionality, empowering them for widespread application in the biomedical realm. However, the properties of fluorinated protein materials remain unpredictable due to the heavy context-dependency of the surrounding atoms influenced by fluorine's strong electron-withdrawing tendencies. This review aims to discern patterns and elucidate design principles governing the biochemical synthesis and rational installation of fluorine into protein and peptide sequences for diverse biomedical applications. Several case studies are presented to deconvolute the overgeneralized fluorous stabilization effect and critically examine the duplicitous nature of the resultant enhanced chemical and thermostability as it applies to use as biomimetic therapeutics, drug delivery vehicles, and bioimaging modalities.
氟化是赋予生物大分子独特功能的最强大的现代设计策略之一,使它们能够在生物医学领域广泛应用。然而,由于氟的强吸电子倾向对周围原子的强烈背景依赖性,氟化蛋白质材料的性质仍然不可预测。本综述旨在识别模式并阐明设计原则,这些原则支配着氟在蛋白质和肽序列中的生化合成以及合理引入,以用于各种生物医学应用。文中给出了几个案例研究,以剖析过度概括的氟稳定化效应,并批判性地审视由此产生的增强化学稳定性和热稳定性的双重性质,因为它适用于作为仿生治疗剂、药物递送载体和生物成像模式。