Chatterjee Chiradip, Gerig John T
Department of Chemistry and Biochemistry, University of California, Santa Barbara, CA 93106, USA.
Biopolymers. 2007;87(2-3):115-23. doi: 10.1002/bip.20796.
It has been suggested that aggregation of fluorinated alcohols in water solutions is involved with the abilities of these alcohols to provoke conformational changes in peptides and proteins. The extent of fluoroalcohol aggregation depends on the degree of fluorination: hexafluoroisopropanol (HFIP) is more extensively aggregated than is TFE. We previously described a study of the interactions of HFIP with the peptide Trp-cage and provided evidence for the formation of long-lived complexes between this fluoroalcohol and the peptide. In the present work, we have examined the interactions of the less-fluorinated TFE with Trp-cage, in order to probe the role of fluoroalcohol aggregation in the phenomena observed. Intermolecular (1)H{(19)F} nuclear Overhauser effects arising from interactions of TFE with the hydrogens of the peptide in a solution containing 42% TFE were determined at sample temperatures from 5 to 45 degrees C. It is shown that the folded state of the peptide under these conditions is essentially the same as that observed in water and in 30% HFIP-water. The observed peptide-solvent NOEs indicate formation of complexes of Trp-cage with TFE that persist for times of the order of 1 ns. The interactions leading to complexes with TFE are somewhat weaker than those involved in complex formation with HFIP. There are no indications that the aggregation of fluoroalcohol is a necessary concomitant of the interactions of TFE or HFIP with Trp-cage. Rather, the stronger and more long-lived interactions of HFIP with Trp-cage appear to be primarily the result of the greater hydrogen-bonding ability and hydrophobicity of this fluoroalcohol.
有人提出，含氟醇在水溶液中的聚集与这些醇引起肽和蛋白质构象变化的能力有关。含氟醇的聚集程度取决于氟化程度：六氟异丙醇（HFIP）比三氟乙醇（TFE）的聚集程度更高。我们之前描述了一项关于HFIP与肽Trp-cage相互作用的研究，并提供了证据证明这种含氟醇与该肽之间形成了长寿命复合物。在本工作中，我们研究了氟化程度较低的TFE与Trp-cage的相互作用，以探究含氟醇聚集在观察到的现象中的作用。在5至45摄氏度的样品温度下，测定了在含有42% TFE的溶液中TFE与肽的氢相互作用产生的分子间（1）H{(19)F}核Overhauser效应。结果表明，在这些条件下肽的折叠状态与在水中和30% HFIP-水体系中观察到的基本相同。观察到的肽-溶剂核Overhauser效应表明Trp-cage与TFE形成了持续时间约为1 ns的复合物。导致与TFE形成复合物的相互作用比与HFIP形成复合物的相互作用稍弱。没有迹象表明含氟醇的聚集是TFE或HFIP与Trp-cage相互作用的必然伴随现象。相反，HFIP与Trp-cage更强且更持久的相互作用似乎主要是由于这种含氟醇具有更强的氢键形成能力和疏水性。
