Ternary System of Solution Additives with Arginine and Salt for Refolding of Beta-Galactosidase

Fujimoto, Akiko; Hirano, Atsushi; Shiraki, Kentaro

doi:10.1007/s10930-010-9235-7

Cited by 12 publications

(7 citation statements)

References 46 publications

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“…We have also shown that Arg enhances refolding of monomeric [10] and oligomeric proteins [19], and inhibits heat-induced aggregation [9],[10],[12],[13]. It has been suggested that such effects of Arg are due to the ability to solubilize aggregation-prone denatured proteins [20], as also indicated by the enhancement of solubility of hydrophobic small compounds by Arg [21]–[24].…”

Section: Introductionmentioning

confidence: 64%

Arginine Inhibits Adsorption of Proteins on Polystyrene Surface

et al. 2013

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Nonspecific adsorption of protein on solid surfaces causes a reduction of concentration as well as enzyme inactivation during purification and storage. However, there are no versatile inhibitors of the adsorption between proteins and solid surfaces at low concentrations. Therefore, we examined additives for the prevention of protein adsorption on polystyrene particles (PS particles) as a commonly-used material for vessels such as disposable test tubes and microtubes. A protein solution was mixed with PS particles, and then adsorption of protein was monitored by the concentration and activity of protein in the supernatant after centrifugation. Five different proteins bound to PS particles through electrostatic, hydrophobic, and aromatic interactions, causing a decrease in protein concentration and loss of enzyme activity in the supernatant. Among the additives, including arginine hydrochloride (Arg), lysine hydrochloride, guanidine hydrochloride, NaCl, glycine, and glucose, Arg was most effective in preventing the binding of proteins to PS particles as well as activity loss. Moreover, even after the mixing of protein and PS particles, the addition of Arg caused desorption of the bound protein from PS particles. This study demonstrated a new function of Arg, which expands the potential for application of Arg to proteins.

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Section: Introductionmentioning

confidence: 64%

Arginine Inhibits Adsorption of Proteins on Polystyrene Surface

et al. 2013

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“…We have developed the application of ArgHCl for suppressing aggregation and adsorption of various proteins during heat treatment and oxidative refolding (16)(17)(18)(19)(20)(21)(22). These effects have been ascribed, at least in part, to the interaction of aromatic groups on arginine with the protein surface (23).…”

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confidence: 99%

Arginine and lysine reduce the high viscosity of serum albumin solutions for pharmaceutical injection

Inoue

Takai

Arakawa

et al. 2014

Journal of Bioscience and Bioengineering

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Therapeutic protein solutions for subcutaneous injection must be very highly concentrated, which increases their viscosity through protein-protein interactions. However, maintaining a solution viscosity below 50 cP is important for the preparation and injection of therapeutic protein solutions. In this study, we examined the effect of various amino acids on the solution viscosity of very highly concentrated bovine serum albumin (BSA) and human serum albumin (HSA) at a physiological pH. Among the amino acids tested, l-arginine hydrochloride (ArgHCl) and l-lysine hydrochloride (LysHCl) (50-200 mM) successfully reduced the viscosity of both BSA and HSA solutions; guanidine hydrochloride (GdnHCl), NaCl, and other sodium salts were equally as effective, indicating the electrostatic shielding effect of these additives. Fourier transform infrared spectroscopy showed that BSA is in its native state even in the presence of ArgHCl, LysHCl, and NaCl at high protein concentrations. These results indicate that weakened protein-protein interactions play a key role in reducing solution viscosity. ArgHCl and LysHCl, which are also non-toxic compounds, will be used as additives to reduce the solution viscosity of concentrated therapeutic proteins.

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“…After the discovery, Arg has been use for the refolding of many medical proteins, including immunotoxin from monoclonal antibody fused with Pseudomonas exotoxin A [37], truncated tissue-type plasminogen activator [38], rabbit heterotetrameric casein kinase II [39], interleukin-6 receptor [40], Psedomonas fluorescens lipase [41], human neurotrophin-3 [42], human and mouse single-chain Fv fragments [43], human interleukin-21 [44], and human interleukin-10 [45]. Furthermore, Arg-assisted refolding technology has been practically enhanced for "step-wise dilution" [46], the synergistic effect of Arg with kosmotropic ions [47] or a weak detergent of lauroyl-L-glutamate and Arg [48] and on the column refolding of a monomeric noncollagenous domain of Type IV collagen [49].…”

Section: Arginine Is a Versatile Additive That Prevents Physical Aggrmentioning

confidence: 99%

“…Similarly, Arg promotes heat-induced aggregation for the large immunoglobulin G1 protein [82] and the β-lactoglobulin (βLG) oligomeric protein [74]. Such structurally unstable proteins can be stabilized by the use of Arg with the acidic amino acids Glu and Asp [82] and the kosmotropic ions [47]. Thus, it is possible that Arg promotes the heat-induced aggregation of large and complex proteins at low concentration.…”

Section: Arginine Is a Versatile Additive That Prevents Physical Aggrmentioning

confidence: 99%

Small Amine Molecules: Solvent Design Toward Facile Improvement of Protein Stability Against Aggregation and Inactivation

Shiraki

Tomita²,

Inoue³

2015

CPB

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Proteins are prone to inactivation in aqueous solutions because chemical modification and aggregation usually occur, particularly at high temperature. This review focuses on the recent advance in practical application with amine compounds that prevent the heat-induced inactivation and aggregation of proteins. Coexistence of amine solutes, typically diamines, polyamines, amino acid esters, and amidated amino acids decreases the heat-induced inactivation rate of proteins by one order of magnitude compared with that in the absence of additives under low concentrations of proteins at physiological pH. The amine compounds mainly suppress chemical modification, typically the β-elimination of disulfide bond and deamidation of asparagine side chain, thereby preventing heat-induced inactivation of proteins. Polyamines do not improve the refolding yield of proteins, owing to decrease in the solubility of unfolded proteins. In contrast, arginine is the most versatile additive for various situations, such as refolding of recombinant proteins, solubilized water-insoluble compounds, and prevention of nonspecific binding to solid surfaces; however, it is not always effective for preventing heat-induced aggregation. Amine compounds will be a key to prevent protein inactivation in solution additives.

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Ternary System of Solution Additives with Arginine and Salt for Refolding of Beta-Galactosidase

Cited by 12 publications

References 46 publications

Arginine Inhibits Adsorption of Proteins on Polystyrene Surface

Arginine Inhibits Adsorption of Proteins on Polystyrene Surface

Arginine and lysine reduce the high viscosity of serum albumin solutions for pharmaceutical injection

Small Amine Molecules: Solvent Design Toward Facile Improvement of Protein Stability Against Aggregation and Inactivation

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