Wrap-and-Strip Technology of Protein–Polyelectrolyte Complex for Biomedical Application

Shiraki, Kentaro; Kurinomaru, Takaaki; Tomita, Shunsuke

doi:10.2174/0929867323666151127201126

Cited by 14 publications

(9 citation statements)

References 111 publications

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“…The precipitated-state PPC is stable for heat, oxidation, and agitation [ 128 ] and is nontoxic [ 129 ]. Thus, the emulsion-state PPC will be a new candidate for the formulation of high-concentration protein to suppress the viscosity of the solution [ 130 ].…”

Section: Cluster and Aggregatesmentioning

confidence: 99%

Viscosity Control of Protein Solution by Small Solutes: A Review

Hong

Iwashita

Shiraki

2018

CPPS

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100

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Viscosity of protein solution is one of the most troublesome issues for the high-concentration formulation of protein drugs. In this review, we summarize the practical methods that suppress the viscosi-ty of protein solution using small molecular additives. The small amount of salts decreases the viscosity that results from electrostatic repulsion and attraction. The chaotrope suppresses the hydrophobic attraction and cluster formation, which can lower the solution viscosity. Arginine hydrochloride (ArgHCl) also sup-presses the solution viscosity due to the hydrophobic and aromatic interactions between protein molecules. The small molecular additives are the simplest resolution of the high viscosity of protein solution as well as understanding of the primary cause in complex phenomena of protein interactions.

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Section: Cluster and Aggregatesmentioning

confidence: 99%

Viscosity Control of Protein Solution by Small Solutes: A Review

Hong

Iwashita

Shiraki

2018

CPPS

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100

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“…Protein-PE complexes are being implemented in various industrial and biotechnological applications ranging from protein purification [ 3 , 4 , 5 , 6 ], enzyme activation [ 7 ], drug delivery [ 8 , 9 , 10 ], biosensors [ 11 ], stabilization in food emulsions [ 12 ] etc. Protein-PE interactions are also important in in vivo processes such as the formation of membraneless organelles [ 5 , 13 ] through liquid-liquid phase separation or the interaction between natural polyelectrolytes (DNA) and proteins (histones) [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Modulating Role of Co-Solutes in Complexation between Bovine Serum Albumin and Sodium Polystyrene Sulfonate

Simončič

Lukšič

2022

Polymers

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The action of three types of co-solutes: (i) salts (NaCl, NaBr, NaI), (ii) polymer (polyethylene glycol; PEG-400, PEG-3000, PEG-20000), and (iii) sugars (sucrose, sucralose) on the complexation between bovine serum albumin (BSA) and sodium polystyrene sulfonate (NaPSS) was studied. Three critical pH parameters were extracted from the pH dependence of the solution’s turbidity: pHc corresponding to the formation of the soluble complexes, pHΦ corresponding to the formation of the insoluble complexes, and pHopt corresponding to the charge neutralization of the complexes. In the presence of salts, the formation of soluble and insoluble complexes as well as the charge neutralization of complexes was hindered, which is a consequence of the electrostatic screening of attractive interactions between BSA and NaPSS. Distinct anion-specific trends were observed in which the stabilizing effect of the salt increased in the order: NaCl < NaBr < NaI. The presence of PEG, regardless of its molecular weight, showed no measurable effect on the formation of soluble complexes. PEG-400 and PEG-3000 showed no effect on the formation of insoluble complexes, but PEG-20000 in high concentrations promoted their formation due to the molecular crowding effect. The presence of sugar molecules had little effect on BSA-NaPSS complexation. Sucralose showed a minor stabilizing effect with respect to the onset of complex formation, which was due to its propensity to the protein surface. This was confirmed by the fluorescence quenching assay (Stern-Volmer relationship) and all-atom MD simulations. This study highlights that when evaluating the modulatory effect of co-solutes on protein-polyelectrolyte interactions, (co-solute)-protein interactions and their subsequent impact on protein aggregation must also be considered.

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“…Polyelectrolytes of high linear charge density but carrying no more than one charged group in the repeat unit, specifically conventional vinylic polyions, are well characterized and widely used in biotechnology and medicine, e.g., for the separation of multicomponent protein systems, , protein stabilization, , immobilization, − or the delivery of cargo nucleic acids into the cell. , The information on polyelectrolytes with a higher charge density, specifically bearing two ionic or ionogenic groups in the repeat unit, is rather scant. Meanwhile, there are grounds for believing that such “supercharged” polyelectrolytes are prone to binding efficiently with oppositely charged polymers, in particular enzymes and nucleic acids, − yielding (bio)polylectrolyte complexes.…”

Section: Introductionmentioning

confidence: 99%

Supercharged Polyplexes: Full-Atom Molecular Dynamics Simulations and Experimental Study

2018

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Quite recently, we reported the synthesis of supercharged polycations bearing pH-insensitive doublecharged repeat units with either three or five methylene groups in the space between charges. The developed approach is based on the quaternization of the parent poly(4-vinylpyridine) with different alkylating agents, providing the possibility to perform the modification as a one-step reaction, which occurs in mild conditions with a controllable degree of conversion. In the present work, we used the above approach for preparing and investigating supercharged polyplexes (polyelectrolyte complexes of nucleic acids), in particular to elucidate the reason for the key feature, i.e., the clearly defined stability of the polyplexes formed by supercharged polyamines. The main findings of the experimental study were confirmed by the results of full atomic modeling, and the principal regularities responsible for the structure, stability, and properties of the supercharged polyplexes have been elucidated for the first time.

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Wrap-and-Strip Technology of Protein–Polyelectrolyte Complex for Biomedical Application

Abstract: A polyelectrolyte is a polymer composed of repeating units of an electrolyte group that enables reversible complex formation with proteins in aqueous solutions. This review introduces "wrap-and-strip"

Cited by 14 publications

References 111 publications

Viscosity Control of Protein Solution by Small Solutes: A Review

Viscosity Control of Protein Solution by Small Solutes: A Review

Modulating Role of Co-Solutes in Complexation between Bovine Serum Albumin and Sodium Polystyrene Sulfonate

Supercharged Polyplexes: Full-Atom Molecular Dynamics Simulations and Experimental Study

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