Biophysical and Biomaterials Research Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India.
J Phys Chem Lett. 2021 Feb 25;12(7):1803-1813. doi: 10.1021/acs.jpclett.0c03492. Epub 2021 Feb 12.
Naturally occurring osmoprotectants are known to prevent aggregation of proteins under various stress factors including extreme pH and elevated temperature conditions. Here, we synthesized gold nanoparticles coated with selected osmolytes (proline, hydroxyproline, and glycine) and examined their effect on temperature-induced amyloid-formation of insulin hormone. These uniform, thermostable, and hemocompatible gold nanoparticles were capable of inhibiting both spontaneous and seed-induced amyloid aggregation of insulin. Both quenching and docking experiments suggest a direct interaction between the osmoprotectant-coated nanoparticles and aggregation-prone hydrophobic stretches of insulin. Circular-dichroism results confirmed the retention of insulin's native structure in the presence of these nanoparticles. Unlike the indirect solvent-mediated effect of free osmolytes, the inhibition effect of osmolyte-coated gold nanoparticles was observed to be mediated through their direct interaction with insulin. The results signify the protection of the exposed aggregation-prone domains of insulin from temperature-induced self-assembly through osmoprotectant-coated nanoparticles, and such effect may inspire the development of osmolyte-based antiamyloid nanoformulations.
天然存在的渗透调节剂已知可预防各种应激因素（包括极端 pH 值和高温条件）下蛋白质的聚集。在这里，我们合成了用选定的渗透调节剂（脯氨酸、羟脯氨酸和甘氨酸）包被的金纳米粒子，并研究了它们对胰岛素激素温度诱导的淀粉样形成的影响。这些均匀、热稳定和血液相容的金纳米粒子能够抑制胰岛素的自发和种子诱导的淀粉样聚集。猝灭和对接实验表明，渗透调节剂包被的纳米粒子与胰岛素中易于聚集的疏水性伸展部分之间存在直接相互作用。圆二色性结果证实了这些纳米粒子存在时胰岛素的天然结构得以保留。与游离渗透调节剂的间接溶剂介导效应不同，观察到渗透调节剂包被的金纳米粒子的抑制作用是通过它们与胰岛素的直接相互作用介导的。这些结果表明，通过渗透调节剂包被的纳米粒子可以保护胰岛素中暴露的易于聚集的结构域免受温度诱导的自组装，这种作用可能激发基于渗透调节剂的抗淀粉样纳米制剂的发展。
