Okada Shunsuke, Matsusaki Motonori, Okumura Masaki, Muraoka Takahiro
Department of Applied Chemistry, Graduate School of Engineering, Tokyo University of Agriculture and Technology, 2-24-16 Naka-cho, Koganei, Tokyo 184-8588, Japan.
Frontier Research Institute for Interdisciplinary Sciences, Tohoku University, 6-3 Aramaki-Aza-Aoba, Aoba-ku, Sendai 980-8578, Japan.
Molecules. 2021 Feb 7;26(4):879. doi: 10.3390/molecules26040879.
Oxidative protein folding is a biological process to obtain a native conformation of a protein through disulfide-bond formation between cysteine residues. In a cell, disulfide-catalysts such as protein disulfide isomerase promote the oxidative protein folding. Inspired by the active sites of the disulfide-catalysts, synthetic redox-active thiol compounds have been developed, which have shown significant promotion of the folding processes. In our previous study, coupling effects of a thiol group and guanidyl unit on the folding promotion were reported. Herein, we investigated the influences of a spacer between the thiol group and guanidyl unit. A conjugate between thiol and guanidyl units with a diethylene glycol spacer (GdnDEG-SH) showed lower folding promotion effect compared to the thiol-guanidyl conjugate without the spacer (GdnSH). Lower acidity and a more reductive property of the thiol group of GdnDEG-SH compared to those of GdnSH likely resulted in the reduced efficiency of the folding promotion. Thus, the spacer between the thiol and guanidyl groups is critical for the promotion of oxidative protein folding.
氧化蛋白质折叠是一个通过半胱氨酸残基之间形成二硫键来获得蛋白质天然构象的生物学过程。在细胞中，诸如蛋白质二硫键异构酶之类的二硫键催化剂促进氧化蛋白质折叠。受二硫键催化剂活性位点的启发，已开发出合成的氧化还原活性硫醇化合物，这些化合物已显示出对折叠过程有显著促进作用。在我们之前的研究中，报道了硫醇基团和胍基单元对折叠促进的耦合效应。在此，我们研究了硫醇基团和胍基单元之间间隔基团的影响。与没有间隔基团的硫醇 - 胍基共轭物（GdnSH）相比，具有二甘醇间隔基团的硫醇和胍基单元之间的共轭物（GdnDEG - SH）显示出较低的折叠促进效果。与GdnSH相比，GdnDEG - SH的硫醇基团较低的酸度和更强的还原性可能导致折叠促进效率降低。因此，硫醇基团和胍基之间的间隔基团对于促进氧化蛋白质折叠至关重要。
