Wawer Jarosław, Krakowiak Joanna, Szociński Michał, Lustig Zofia, Olszewski Marcin, Szostak Kamila
Department of Physical Chemistry, Faculty of Chemistry, Gdańsk University of Technology, Narutowicza Str. 11/12, 80-233 Gdańsk, Poland.
Department of Physical Chemistry, Faculty of Chemistry, Gdańsk University of Technology, Narutowicza Str. 11/12, 80-233 Gdańsk, Poland.
Int J Biol Macromol. 2014 Sep;70:214-21. doi: 10.1016/j.ijbiomac.2014.06.057. Epub 2014 Jul 7.
In vitro inhibition of the formation of fibrous aggregates of proteins (amyloids) has gained increasing attention due to the number of diseases associated with protein misfolding and fibrillation. An interesting group of compounds for which pronounced activity against this phenomenon can be expected consists of low molecular weight substances (osmolytes) which have the ability to change protein stability. Here we investigate the influence of trimethylamine N-oxide (TMAO) in acidic solution (pH=2) on the fibrillation of hen egg white lysozyme (HEWL). The process was monitored by five techniques: circular dichroism in the UV region, atomic force microscopy, dynamic light scattering, densimetry and gel electrophoresis. The obtained results show that protonated TMAO in a concentration of 400 mM inhibits amyloidogenesis. In the conditions of the experiment the HEWL molecules form clusters about 30 nm in diameter containing a relatively high fraction of covalent-bonded dimers.
由于与蛋白质错误折叠和纤维化相关的疾病数量众多，体外抑制蛋白质纤维聚集体（淀粉样蛋白）的形成受到了越来越多的关注。一类有望对这种现象具有显著活性的有趣化合物是低分子量物质（渗透溶质），它们具有改变蛋白质稳定性的能力。在此，我们研究了酸性溶液（pH = 2）中三甲胺 N-氧化物（TMAO）对鸡蛋清溶菌酶（HEWL）纤维化的影响。通过五种技术监测该过程：紫外区域的圆二色性、原子力显微镜、动态光散射、密度测定法和凝胶电泳。所得结果表明，浓度为 400 mM 的质子化 TMAO 可抑制淀粉样蛋白生成。在实验条件下，HEWL 分子形成直径约 30 nm 的簇，其中含有相对较高比例的共价键二聚体。
