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Exploring the Counteracting and Refolding Ability of Choline-Based Ionic Liquids toward Crowding Environment-Induced Changes in HSA Structure

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journal contribution
posted on 24.12.2020, 16:07 by Kavya Bhakuni, Anamika Sindhu, Meena Bisht, Pannuru Venkatesu
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.

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