Sekowski Szymon, Ionov Maksim, Abdulladjanova Nodira, Makhmudov Rustam, Mavlyanov Saidmukhtar, Milowska Katarzyna, Bryszewska Maria, Zamaraeva Maria
Department of Biophysics, Laboratory of Molecular Biophysics, Faculty of Biology and Chemistry, University of Bialystok, 15-950 Bialystok, Poland.
Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 90-236 Lodz, Poland.
Colloids Surf B Biointerfaces. 2017 Jul 1;155:159-165. doi: 10.1016/j.colsurfb.2017.04.007. Epub 2017 Apr 10.
The etiology of Parkinson's disease (PD) relates to α-synuclein, a small protein with the ability to aggregate and form Lewy bodies. One of its prevention strategies is inhibition of α-synuclein oligomerization. We have investigated the interaction of α-synuclein and human serum albumin with 3,6-bis-О-di-О-galloyl-1,2,4-tri-О-galloyl-β-d-glucose (a tannin isolated from the plant Rhus typhina). Using fluorescence spectroscopy method we found that this tannin interacts strongly with α-synuclein forming complexes. Circular dichroism analysis showed a time-dependent inhibition of α-synuclein aggregation in the presence of the tannin. On the other hand, 3,6-bis-О-di-О-galloyl-1,2,4-tri-О-galloyl-β-d-glucose had a much stronger interaction with human serum albumin than α-synuclein. The calculated binding constant for tannin-protein interaction was considerably higher for albumin than α-synuclein. This tannin interacted with albumin through a "sphere of action" mechanism. The results lead to the conclusion that 3,6-bis-О-di-О-galloyl-1,2,4-tri-О-galloyl-β-d-glucose is a potent preventive compound against Parkinson's disease. However, this tannin interacts very strongly with human serum albumin, significantly reducing the bioavailability of this compound.
帕金森病（PD）的病因与α-突触核蛋白有关，α-突触核蛋白是一种具有聚集能力并能形成路易小体的小蛋白质。其预防策略之一是抑制α-突触核蛋白的寡聚化。我们研究了α-突触核蛋白和人血清白蛋白与3,6-双-O-二-O-没食子酰基-1,2,4-三-O-没食子酰基-β-D-葡萄糖（从植物盐肤木中分离出的一种单宁）之间的相互作用。使用荧光光谱法，我们发现这种单宁与α-突触核蛋白强烈相互作用形成复合物。圆二色性分析表明，在单宁存在下，α-突触核蛋白的聚集受到时间依赖性抑制。另一方面，3,6-双-O-二-O-没食子酰基-1,2,4-三-O-没食子酰基-β-D-葡萄糖与人血清白蛋白的相互作用比与α-突触核蛋白的相互作用强得多。计算得出的单宁与蛋白质相互作用的结合常数，白蛋白比α-突触核蛋白高得多。这种单宁通过“作用球”机制与白蛋白相互作用。结果得出结论，3,6-双-O-二-O-没食子酰基-1,2,4-三-O-没食子酰基-β-D-葡萄糖是一种有效的帕金森病预防化合物。然而，这种单宁与人血清白蛋白的相互作用非常强烈，显著降低了该化合物的生物利用度。
