Exploring the Counteracting and Refolding Ability of Choline-Based Ionic Liquids toward Crowding Environment-Induced Changes in HSA Structure,ACS Sustainable Chemistry & Engineering

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Exploring the Counteracting and Refolding Ability of Choline-Based Ionic Liquids toward Crowding Environment-Induced Changes in HSA Structure
ACS Sustainable Chemistry & Engineering ( IF 7.1 ) Pub Date : 2020-12-24 , DOI: 10.1021/acssuschemeng.0c07550
Kavya Bhakuni ₁ , Anamika Sindhu ₁ , Meena Bisht ₁ , Pannuru Venkatesu ₁

Affiliation

Human serum albumin (HSA) attracts a great deal of scientific interest for drug discovery and development of novel biologically active molecules. Over the past few years, there has been an increased demand to consider ionic liquids (ILs) as novel biocompatible cosolvents for proteins. While there exist multiple studies on HSA with ILs, HSA remains greatly unexplored with respect to the variation of chain length and functional group of a variety of cholinium-based ILs and their ability for refolding and counteraction of crowding-induced unfolding of HSA. Furthermore, most of the studies are performed in dilute buffers, which is highly inconsistent with in vivo conditions. The intracellular environment is extremely crowded owing to the existence of a variety of macromolecules such as proteins, nucleic acids, ribosomes, carbohydrates, etc. Thus, this article explores the biocompatibility of a series of cholinium-based ILs, namely, choline malonate (Mal), choline propionate (Prop), choline bitartrate (Bit), choline citrate (Cit), and choline dihydrogen phosphate (Dhp) on HSA using various spectroscopic techniques in combination with dynamic light scattering studies. On the basis of the outcome of the current study, most of the biocompatible ILs, i.e., Bit and Dhp, are selected to revoke the effect of a crowding agent, namely, dextran 6 kDa (dex6) on HSA at a fixed concentration. Both the ILs Bit as well as Dhp successfully counteract the crowding effects on the HSA structure. Furthermore, Bit and Dhp showed positive results for refolding of the dex6-perturbed HSA structure. Intriguingly, it was also observed that the stabilizing effect of ILs was more profound under crowded conditions compared to an IL alone.

中文翻译：

探索胆碱基离子液体对拥挤环境引起的HSA结构变化的抵消和重折叠能力

人血清白蛋白（HSA）对于药物发现和新型生物活性分子的开发引起了极大的科学兴趣。在过去的几年中，对离子液体（ILs）作为蛋白质的新型生物相容性助溶剂的需求不断增加。尽管关于IL的HSA已有多项研究，但关于各种基于胆碱的IL的链长和官能团的变化及其重折叠和拥挤诱导的HSA展开反作用的能力，HSA仍未开发。此外，大多数研究是在稀缓冲液中进行的，这与体内高度不一致条件。由于存在多种大分子，例如蛋白质，核酸，核糖体，碳水化合物等，细胞内环境非常拥挤。因此，本文探讨了一系列基于胆碱的ILs（丙二酸胆碱）的生物相容性。），HSA上的丙酸胆碱（Prop），酒石酸胆碱（Bit），柠檬酸胆碱（Cit）和磷酸胆碱二氢磷酸酯（Dhp）结合各种光谱技术与动态光散射研究相结合。根据当前研究的结果，选择了大多数生物相容性IL（即Bit和Dhp）以消除固定浓度的拥塞剂（即葡聚糖6 kDa（dex6））对HSA的作用。IL位和Dhp都成功地抵消了对HSA结构的拥挤效应。此外，Bit和Dhp对于被dex6干扰的HSA结构的折叠显示了积极的结果。有趣的是，与单独的IL相比，在拥挤的条件下IL的稳定作用更为明显。

更新日期：2021-01-11

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