Aggregative protein–polyelectrolyte complex for high-concentration formulation of protein drugs

Kurinomaru, Takaaki; Shiraki, Kentaro

doi:10.1016/j.ijbiomac.2016.06.016

Cited by 33 publications

(20 citation statements)

References 64 publications

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“…Similarly, an emulsion state of protein–polyelectrolyte complex (PPC) has been developed for the formulation of high-concentration protein drugs [ 125 ]. The molecular mechanism of PPC formation is only from electrostatic interaction.…”

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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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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“…The supernatant of the redissolved solution, including purified CspB fusion protein, is collected (step 5), leaving irreversibly precipitated insoluble impurities. Note that the highly reversible pH-dependent aggregation is used as a protein concentration method [33,34]. When a small amount of buffer is added in steps 3-4, the CspB fusion protein is easily concentrated.…”

Section: Costless Methods Compared With Chromatographymentioning

confidence: 99%

A new pH-responsive peptide tag for protein purification

Nonaka

Tsurui

Mannen

et al. 2018

Protein Expression and Purification

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This paper describes a new pH-responsive peptide tag that adds a protein reversible precipitation and redissolution character. This peptide tag is a part of a cell surface protein B (CspB) derived from Corynebacterium glutamicum. Proinsulin that genetically fused with a peptide of N-terminal 6, 17, 50, or 250 amino acid residues of CspB showed that the reversible precipitation and redissolution depended on the pH. The transition occurred within a physiological and narrow pH range. A CspB50 tag comprising 50 amino acid residues of N-terminal CspB was further evaluated as a representative using other pharmaceutical proteins. Below pH 6.8, almost all CspB50-Teriparatide fusion formed an aggregated state. Subsequent addition of alkali turned the cloudy protein solution transparent above pH 7.3, in which almost all the CspB50-Teriparatide fusion redissolved. The CspB50-Bivalirudin fusion showed a similar behavior with slightly different pH range. This tag is offering a new protein purification method based on liquid-solid separation which does not require an affinity ligand. This sharp response around neutral pH is useful as a pH-responsive tag for the purification of unstable proteins at a non-physiological pH.

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“…High concentration of proteins can also be stored in protein–PE aggregate precipitates [22]. Kurinomaru et al obtained high concentration of proteins (panitumumab, etanercept, thyroglobulin and others) in complexes by precipitation with cationic and anionic PEs (poly-L-lysine and poly-L-glutamic acid) followed by redissolution of the complexes in high salt environments (Figure 6a) without any significant changes in the activities of the proteins and antibodies [114].…”

Section: Protein–polyelectrolyte Bulk Complexesmentioning

confidence: 99%

“…Recent advances in polymer synthesis, biotechnology and characterization techniques coupled with the unique and advantageous attributes of protein–PE complexes have contributed immensely towards the widespread use of bulk phase separated protein–PE complexes in myriad biotechnological applications. These include protein separation, purification and concentration [3,18,19], protein stabilization [20,21,22,23], drug/protein delivery [24,25,26], synthetic bio-adhesives [27,28,29], tissue engineering [30], gene therapy [31] and encapsulants in the food industry [1,32,33].…”

Section: Introductionmentioning

confidence: 99%

Protein–Polyelectrolyte Complexes and Micellar Assemblies

2019

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In this review, we highlight the recent progress in our understanding of the structure, properties and applications of protein–polyelectrolyte complexes in both bulk and micellar assemblies. Protein–polyelectrolyte complexes form the basis of the genetic code, enable facile protein purification, and have emerged as enterprising candidates for simulating protocellular environments and as efficient enzymatic bioreactors. Such complexes undergo self-assembly in bulk due to a combined influence of electrostatic interactions and entropy gains from counterion release. Diversifying the self-assembly by incorporation of block polyelectrolytes has further enabled fabrication of protein–polyelectrolyte complex micelles that are multifunctional carriers for therapeutic targeted delivery of proteins such as enzymes and antibodies. We discuss research efforts focused on the structure, properties and applications of protein–polyelectrolyte complexes in both bulk and micellar assemblies, along with the influences of amphoteric nature of proteins accompanying patchy distribution of charges leading to unique phenomena including multiple complexation windows and complexation on the wrong side of the isoelectric point.

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Aggregative protein–polyelectrolyte complex for high-concentration formulation of protein drugs

Cited by 33 publications

References 64 publications

Viscosity Control of Protein Solution by Small Solutes: A Review

Viscosity Control of Protein Solution by Small Solutes: A Review

A new pH-responsive peptide tag for protein purification

Protein–Polyelectrolyte Complexes and Micellar Assemblies

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