Role of ionic liquids on stabilization of therapeutic proteins and model proteins

Guncheva, Maya

doi:10.1007/s10930-022-10058-5

Cited by 6 publications

(7 citation statements)

References 99 publications

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“…Both of these properties could help to intensify refolding processes and lower their environmental burden by reducing the need of diluting the solubilizate. The influence of the most common IL ions on protein folding has been recently reviewed by Guncheva (2022) .…”

Section: Mild Inclusion Body Solubilizationmentioning

confidence: 99%

State-of-the-art and novel approaches to mild solubilization of inclusion bodies

Klausser,

Kopp,

Prada Brichtova

et al. 2023

Front. Bioeng. Biotechnol.

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Throughout the twenty-first century, the view on inclusion bodies (IBs) has shifted from undesired by-products towards a targeted production strategy for recombinant proteins. Inclusion bodies can easily be separated from the crude extract after cell lysis and contain the product in high purity. However, additional solubilization and refolding steps are required in the processing of IBs to recover the native protein. These unit operations remain a highly empirical field of research in which processes are developed on a case-by-case basis using elaborate screening strategies. It has been shown that a reduction in denaturant concentration during protein solubilization can increase the subsequent refolding yield due to the preservation of correctly folded protein structures. Therefore, many novel solubilization techniques have been developed in the pursuit of mild solubilization conditions that avoid total protein denaturation. In this respect, ionic liquids have been investigated as promising agents, being able to solubilize amyloid-like aggregates and stabilize correctly folded protein structures at the same time. This review briefly summarizes the state-of-the-art of mild solubilization of IBs and highlights some challenges that prevent these novel techniques from being yet adopted in industry. We suggest mechanistic models based on the thermodynamics of protein unfolding with the aid of molecular dynamics simulations as a possible approach to solve these challenges in the future.

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Section: Mild Inclusion Body Solubilizationmentioning

confidence: 99%

State-of-the-art and novel approaches to mild solubilization of inclusion bodies

Klausser,

Kopp,

Prada Brichtova

et al. 2023

Front. Bioeng. Biotechnol.

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“…In contrast, the majority of the studies on the impact of ILs on various proteins concern possible IL applications in biotechnology and thus address the interactions between a particular IL and a particular protein from the viewpoint of stabilizing/destabilizing effects of the former on the latter. ,,− Thus, sometimes it is difficult to discern possible biotechnological advantages or disadvantages of ILs from their deleterious impact on proteins. Therefore, in the corresponding section of the review, we discuss only the most evident cases of inhibitory effects of ILs on proteins, which include the enzymes acetylcholinesterase, citrate synthase, adenosine deaminase, carboxylesterase, and cytochrome c oxidase, as well as the transporter proteins MATE1 and MATE2-K.…”

Section: Mechanisms Of Biological Activity Of Ionic Liquids: State Of...mentioning

confidence: 99%

Mechanisms of Biological Effects of Ionic Liquids: From Single Cells to Multicellular Organisms

Egorova,

Kibardin,

Posvyatenko

et al. 2024

Chem. Rev.

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The review presents a detailed discussion of the evolving field studying interactions between ionic liquids (ILs) and biological systems. Originating from molten salt electrolytes to present multiapplication substances, ILs have found usage across various fields due to their exceptional physicochemical properties, including excellent tunability. However, their interactions with biological systems and potential influence on living organisms remain largely unexplored. This review examines the cytotoxic effects of ILs on cell cultures, biomolecules, and vertebrate and invertebrate organisms. Our understanding of IL toxicity, while growing in recent years, is yet nascent. The established findings include correlations between harmful effects of ILs and their ability to disturb cellular membranes, their potential to trigger oxidative stress in cells, and their ability to cause cell death via apoptosis. Future research directions proposed in the review include studying the distribution of various ILs within cellular compartments and organelles, investigating metabolic transformations of ILs in cells and organisms, detailed analysis of IL effects on proteins involved in oxidative stress and apoptosis, correlation studies between IL doses, exposure times and resulting adverse effects, and examination of effects of subtoxic concentrations of ILs on various biological objects. This review aims to serve as a critical analysis of the current body of knowledge on IL-related toxicity mechanisms. Furthermore, it can guide researchers toward the design of less toxic ILs and the informed use of ILs in drug development and medicine.

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“…Advancing the development of more effective additives for both the unfolding and refolding stages is imperative for future progress in this field [12]. Here, ionic liquids come into play [13].…”

Section: Refolding and Purificationmentioning

confidence: 99%

Inclusion Bodies in Ionic Liquids

Szabadi,

Klausser,

Spadiut

et al. 2023

Liquids

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The pivotal role of proteins in pharmaceuticals is challenged by stability issues, making the study of inclusion bodies—a source of insoluble protein aggregates—increasingly relevant. This review outlines the critical procedures in inclusion body processing, focusing on ’mild solubilization concepts’ and refolding methodologies. Attention is afforded to the emerging role of ionic liquids with unique and tunable physicochemical properties in optimizing protein unfolding and refolding processes. The review critically assesses the existing literature at the intersection of inclusion bodies and ionic liquids, identifying recent advancements, potential applications, and avenues for future research. This comprehensive analysis aims to elucidate the complexities in efficient protein processing from inclusion bodies.

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Role of ionic liquids on stabilization of therapeutic proteins and model proteins

Cited by 6 publications

References 99 publications

State-of-the-art and novel approaches to mild solubilization of inclusion bodies

State-of-the-art and novel approaches to mild solubilization of inclusion bodies

Mechanisms of Biological Effects of Ionic Liquids: From Single Cells to Multicellular Organisms

Inclusion Bodies in Ionic Liquids

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