Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA.
Protein Sci. 2012 Apr;21(4):453-62. doi: 10.1002/pro.2030. Epub 2012 Feb 14.
Fluorocarbons are quintessentially man-made molecules, fluorine being all but absent from biology. Perfluorinated molecules exhibit novel physicochemical properties that include extreme chemical inertness, thermal stability, and an unusual propensity for phase segregation. The question we and others have sought to answer is to what extent can these properties be engineered into proteins? Here, we review recent studies in which proteins have been designed that incorporate highly fluorinated analogs of hydrophobic amino acids with the aim of creating proteins with novel chemical and biological properties. Fluorination seems to be a general and effective strategy to enhance the stability of proteins, both soluble and membrane bound, against chemical and thermal denaturation, although retaining structure and biological activity. Most studies have focused on small proteins that can be produced by peptide synthesis as synthesis of large proteins containing specifically fluorinated residues remains challenging. However, the development of various biosynthetic methods for introducing noncanonical amino acids into proteins promises to expand the utility of fluorinated amino acids in protein design.
全氟化合物本质上是人造分子，几乎不含生物学中的氟。全氟分子表现出新颖的物理化学性质，包括极端的化学惰性、热稳定性和异常的相分离倾向。我们和其他人一直在努力回答的问题是，在多大程度上可以将这些特性设计到蛋白质中？在这里，我们回顾了最近的研究，这些研究设计了含有高度氟化的疏水性氨基酸类似物的蛋白质，旨在创造具有新型化学和生物学特性的蛋白质。氟化似乎是一种通用且有效的策略，可以增强蛋白质的稳定性，无论是可溶性的还是膜结合的，防止化学和热变性，尽管保留了结构和生物活性。大多数研究都集中在可以通过肽合成生产的小蛋白质上，因为合成含有特定氟化残基的大蛋白质仍然具有挑战性。然而，各种将非典型氨基酸引入蛋白质的生物合成方法的发展有望扩大氟代氨基酸在蛋白质设计中的应用。
