Ionic liquids as biocompatible stabilizers of proteins
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REVIEW
Ionic liquids as biocompatible stabilizers of proteins Mouhamad Reslan 1 & Veysel Kayser 1 Received: 8 January 2018 / Accepted: 19 February 2018 # International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag GmbH Germany, part of Springer Nature 2018
Abstract Ionic liquids (ILs) have recently emerged as versatile solvents and additives in the field of biotechnology, particularly as stabilizers of proteins and enzymes. Of interest to the biotechnology industry is the formulation of stable biopharmaceuticals, therapeutic proteins, and vaccines which have revolutionized the treatment of many diseases including debilitating conditions such as cancers and auto-immune diseases. The stabilization of therapeutic proteins is typically achieved using additives that prevent unfolding and aggregation of these proteins during manufacture, transport, and long-term storage. To determine if ILs could be used in the formulation of stable therapeutic proteins, a thorough understanding of the effects of ILs on protein stability is needed, as well as understanding the toxicity of ILs on humans, and other considerations for formulation development such as viscosity and osmolality. In this review, we summarize recent developments on the stabilization of proteins and enzymes using ILs, with emphasis on identifying biocompatible ILs that may be suitable for the formulation of stable biopharmaceuticals in the future. Keywords Protein aggregation . Stability . Toxicity . Formulations . Protein unfolding . Biotechnology
Abbreviations ILs PIL AIL EAN DHP Chol BMIM EMIM PMIM HMIM MMIM SCN Cyt C BSA rPa MDEG
Ionic liquids Protic ionic liquid Aprotic ionic liquid Ethylammonium nitrate Dihydrogen phosphate Choline 1-Butyl-3-methyilimidazolium 1-Ethyl-3-methylimidazolium 1-Methyl-3-propylimidazolium 1-Hexyl-3-methylimidazolium 1,3-Dimethylimidazolium Thiocyanate Cytochrome complex Bovine serum albumin Recombinant plasminogen activator 2(2-Methoxyethoxy)-ethyl
This article is part of a Special Issue on ‘Ionic Liquids and Biomolecules’ edited by Antonio Benedetto and Hans-Joachim Galla. * Veysel Kayser [email protected] 1
Faculty of Pharmacy, The University of Sydney, Sydney, NSW 2006, Australia
HexSO4 Tos OH-EMIM OH-PMIM OH-HMIM BF4 CT BzMIM TEAA TEAP TBPBr Ac Cit rHIL-2 TMA Lac Prop Hex DMP TFMS TF2N Glu GuHCl
Hexylsulfate Tosylate 1-(2-Hydroxyethyl) -3-methylimidazolium 1-(3-Hydroxypropyl) -3-methylimidazolium 1-(6-Hydroxyhexyl) -3-methylimidazolium Tetrafluoroborate α-Chymotrypsinogen 1-Benzyl-3-methylimidazolium Triethylammonium acetate Triethylammonium phosphate Tetrabutylphosphonium bromide Acetate Citrate Recombinant human interleukin-2 Trimethyl acetate Lactate Propionate Hexanoate Dimethyl phosphate Trifluoromethane sulfonate Bis(trifluoromethylsulfonyl)amide Glutarate Guanidine hydrochloride
Biophys Rev
mAb EGFR MD DBP BEH TMP DEP EOOEMIM [EOOEMPy][C12SO4]
Monoclonal antibody Epidermal growth factor receptor Molecular dynamics Dibutyl phosphate Bis(2-ethylhexyl) phosphate Bis(2,4,4-trimethyl
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