Department of Chemistry, State University of New York, College at Geneseo, Geneseo, NY, 14454, USA.
Eur Biophys J. 2013 Jun;42(6):495-501. doi: 10.1007/s00249-013-0902-4. Epub 2013 Apr 30.
Because Congo red (CR) can bind to critical intermediate structural forms of amyloid beta (Aβ), it has been suggested as a potential therapeutic agent against neurodegenerative disorders such as Alzheimer's disease. In this study, the interaction of CR with Aβ(12-28) was investigated by use of isothermal titration calorimetry (ITC). Studies conducted between 15 and 35 °C show that binding of CR to Aβ(12-28) was strongly dependent on temperature, with a decrease in CR-Aβ(12-28) complexation as temperature increases, presumably because of conformational changes within Aβ(12-28) at the highest temperatures, that conceal the CR binding sites. In fact, no CR binding was observed at 35 °C. The binding of CR to Aβ(12-28) was associated with favorable changes in both enthalpy and entropy that resulted in binding constants (K) of between 10(5) and 10(6) M (-1). An early (and more intense) entropy-driven CR disaggregation phase (K ~10(7)-10(8) M (-1)) was observed before the onset of CR-Aβ(12-28) complexation. Only CR disaggregation was observed at 35 °C. These results may provide further insights into the ability of CR to inhibit Aβ toxicity in neurodegenerative diseases.
由于刚果红 (CR) 可以与淀粉样β (Aβ) 的关键中间结构形式结合，因此它被认为是治疗阿尔茨海默病等神经退行性疾病的潜在治疗剂。在这项研究中，使用等温滴定量热法 (ITC) 研究了 CR 与 Aβ(12-28) 的相互作用。在 15 至 35°C 之间进行的研究表明，CR 与 Aβ(12-28) 的结合强烈依赖于温度，随着温度的升高，CR-Aβ(12-28) 络合减少，这可能是因为 Aβ(12-28) 在最高温度下发生构象变化，从而掩盖了 CR 结合位点。实际上，在 35°C 时未观察到 CR 结合。CR 与 Aβ(12-28) 的结合伴随着焓和熵的有利变化，导致结合常数 (K) 在 10(5) 到 10(6) M(-1) 之间。在 CR-Aβ(12-28) 络合之前，观察到早期（更强烈）的熵驱动的 CR 解聚相（K~10(7)-10(8) M(-1))。仅在 35°C 时观察到 CR 解聚。这些结果可能为 CR 抑制神经退行性疾病中 Aβ 毒性的能力提供进一步的见解。
