Institute of Biostructures and Bioimaging, National Research Council (CNR), Via Mezzocannone 16, 80134 Naples, Italy.
Cirpeb, InterUniversity Research Centre on Bioactive Peptides, University of Naples "Federico II", Via Mezzocannone 16, 80134 Naples, Italy.
Curr Protein Pept Sci. 2019;20(5):425-451. doi: 10.2174/1389203720666190214152439.
The fluorinated alcohol 2,2,2-Trifluoroethanol (TFE) has been implemented for many decades now in conformational studies of proteins and peptides. In peptides, which are often disordered in aqueous solutions, TFE acts as secondary structure stabilizer and primarily induces an α -helical conformation. The exact mechanism through which TFE plays its stabilizing roles is still debated and direct and indirect routes, relying either on straight interaction between TFE and molecules or indirect pathways based on perturbation of solvation sphere, have been proposed. Another still unanswered question is the capacity of TFE to favor in peptides a bioactive or a native-like conformation rather than simply stimulate the raise of secondary structure elements that reflect only the inherent propensity of a specific amino-acid sequence. In protein studies, TFE destroys unique protein tertiary structure and often leads to the formation of non-native secondary structure elements, but, interestingly, gives some hints about early folding intermediates. In this review, we will summarize proposed mechanisms of TFE actions. We will also describe several examples, in which TFE has been successfully used to reveal structural properties of different molecular systems, including antimicrobial and aggregation-prone peptides, as well as globular folded and intrinsically disordered proteins.
氟代醇 2,2,2-三氟乙醇（TFE）现已在蛋白质和肽的构象研究中使用了数十年。在通常在水溶液中无序的肽中，TFE 作为二级结构稳定剂，主要诱导α-螺旋构象。TFE 发挥稳定作用的确切机制仍存在争议，直接和间接途径，依赖于 TFE 与分子之间的直接相互作用或基于溶剂化球扰动的间接途径，都已经被提出。另一个尚未解决的问题是 TFE 能否有利于肽形成生物活性或类似天然的构象，而不仅仅是刺激二级结构元件的增加，这些二级结构元件仅反映特定氨基酸序列的固有倾向。在蛋白质研究中，TFE 破坏独特的蛋白质三级结构，通常导致形成非天然的二级结构元件，但有趣的是，它给出了一些关于早期折叠中间体的线索。在这篇综述中，我们将总结 TFE 作用的提出机制。我们还将描述几个例子，其中 TFE 已成功用于揭示不同分子系统的结构特性，包括抗菌和易于聚集的肽以及球状折叠和固有无序的蛋白质。
