A coiled coil with a fluorous core
A coiled coil with a fluorous core
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DOI：
10.1021/ja002961j
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发表时间：
2001-05-16
影响因子：
15
通讯作者：
Kumar, K
中科院分区：
文献类型：
--
作者：
Bilgiçer, B;Fichera, A;Kumar, K
设计，合成和结构表征的高度氟化的肽系统的基础上卷曲螺旋区的酵母转录因子GCN 4的描述。所有四个亮氨酸残基（a位置）和三个缬氨酸残基（d位置）分别被非天然氨基酸5，5，5-三氟亮氨酸和4，4，4-三氟缬氨酸替代。通过圆二色性光谱判断，该肽在低微摩尔浓度下是高度α-螺旋的，在5-30 μ M浓度范围内作为二聚体物质沉积，并且显示出比具有烃核的对照肽高15 ℃的二聚体解链温度.此外，从盐酸胍变性实验计算的展开的表观自由能为氟化肽比其烃对应物大1.0千卡/摩尔。我们得出结论，额外的稳定性是来自螯合更疏水的三氟甲基基团从水性溶剂。这些研究介绍了一种新的模式，在分子自组装系统的设计，一个基于正交的液相溶解度特性。
The design, synthesis, and structural characterization of a highly fluorinated peptide system based on the coiled coil region of the yeast transcription factor GCN4 is described. All four leucine residues (a position) and three valine residues (d position) were replaced by the unnatural amino acids 5,5,5-trifluoroleucine and 4,4,4-trifluorovaline, respectively. The peptide is highly alpha -helical at low micromolar concentrations as judged by circular dichroism spectra, sediments as a dimeric species in the 5-30 muM concentration range, and exhibits a dimer melting temperature that is 15 degreesC higher than a control peptide with a hydrocarbon core. Furthermore, the apparent free energy of unfolding as calculated from guanidinium hydrochloride denaturation experiments is larger by 1.0 kcal/mol for the fluorinated peptide than its hydrocarbon counterpart. We conclude that additional stability is derived from sequestering the more hydrophobic trifluoromethyl groups from aqueous solvent. These studies introduce a new paradigm in the design of molecular self-assembling systems, one based on orthogonal solubility properties of liquid phases.