Control of Peptide Structure and Recognition by Fe(III)-Induced Helix Destabilization

Helical peptide segments that change their conformation due to external stimuli have often been
employed in peptide-based molecular devices and materials. Using helices containing a pair of the
iminodiacetic acid derivatives of lysine (Ida), we show that metal-induced helix destabilization is a promising
approach to functional switching, especially for helices that are intrinsically stable. By i and i + 2 positioning
of the Ida residues in a 17-residue model peptide, a significant decrease in the helical content was observed
by the addition of Fe(III), whereas Fe(II) had no influence on the stability of the helix. The possibility of
redox control of the helical structure was exemplified by the reduction of Fe(III) to Fe(II) using Na2S2O4
followed by the subsequent reoxidation. Mutual recognition of the transcription factor Jun-derived leucine-zipper peptide segment with the Fos leucine-zipper segment containing Ida residues was also modulated
in the presence of Fe(III).

受外部刺激后构象发生改变的螺旋肽段 (helical peptide segments)，常被应用于肽基分子器件与材料领域。本研究采用含有一对赖氨酸亚氨基二乙酸衍生物 (iminodiacetic acid derivatives of lysine，简称Ida) 的螺旋肽，证实金属诱导的螺旋失稳是实现功能开关的极具潜力的策略，对于本征稳定的螺旋肽而言尤为如此。在17残基模型肽中，将Ida残基置于i与i+2位后，加入三价铁 (Fe(III)) 可使该肽的螺旋含量显著降低；而二价铁 (Fe(II)) 则对该螺旋的稳定性无影响。通过连二亚硫酸钠 (Na₂S₂O₄) 将三价铁还原为二价铁，随后再进行氧化复性，我们验证了氧化还原调控螺旋结构的可行性。转录因子 (transcription factor) Jun衍生的亮氨酸拉链 (leucine-zipper) 肽段，与携带Ida残基的Fos亮氨酸拉链肽段之间的相互识别作用，在三价铁存在时同样受到调控。