A Model for the Prediction of Precipitation Curves for Globular Proteins with Nonionic Polymers as the Precipitating Agent

Guo, Meining; Narsimhan, Ganesan

doi:10.1080/01496399608001010

Cited by 6 publications

(1 citation statement)

References 25 publications

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“…The solubility data of protein for different PEG molecular weight were reported by the pioneering study of Atha−Ingham . These data were analyzed with different and more or less accurate excluded volume descriptions. ,− Second virial coefficients ( B 2 ) in lysozyme−PEG−water systems, recently presented by Zukoski, showed that the excluded volume, described through an Asakura−Osawa protein−protein potential, cannot justify the nonmonotone concentration dependence of B 2 . On the other hand the PRISM approach, dealing with the nonspherical but segmental structure of the PEG, provided a better explanation.…”

Section: Introductionmentioning

confidence: 99%

Mechanism of Protein−Poly(ethylene glycol) Interaction from a Diffusive Point of View

2002

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The first multicomponent diffusion data ever determined in protein−polymer systems are presented for the system lysozyme(1)−PEG 400(2)−water. Although there are no specific interactions between protein and polymer, the cross-term diffusion coefficient D 21, that links the PEG flow to the protein concentration gradient, is up to 35 times the main-term diffusion coefficient of the protein. This observation can only be due to a “crowding effect” and not to specific interactions, such as electrostatic ones. The exclusion effect is also qualitatively confirmed by the measured counter-flow associated with the protein motion. On the base of a hard core potential, our recent predictive equations are used to predict diffusion coefficients in this ternary system, and a good agreement with the experimental D 21 is obtained. The PEG concentration dependence of the main-term diffusion coefficient of the protein cannot be interpreted exclusively by the excluded volume effect. Some dielectric effect or aggregation phenomena must be invoked to completely describe diffusive behavior in protein−PEG systems. A strong dielectric constant decrease and an anomalous pH dependence on PEG concentration in this system have been observed. We have extended to this nonelectrolyte system a recent procedure for extracting thermodynamic data from ternary diffusion coefficients that uses the Onsager reciprocal relations and the coupling of D ij and second virial coefficient data. Thus we obtained the change of the lysozyme chemical potential with increasing PEG concentration. We emphasize that it is incorrect to neglect the nonideality of PEG−water systems, as was done in some previous preferential solvation analyses.

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Section: Introductionmentioning

confidence: 99%

Mechanism of Protein−Poly(ethylene glycol) Interaction from a Diffusive Point of View

2002

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Protein Aggregation, Denaturation

Schein

1999

Encyclopedia of Bioprocess Technology

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Protein Aggregation and Precipitation, Measurement and Control

Schein

2010

Encyclopedia of Industrial Biotechnology

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Aggregation is both a blessing and a curse to the biochemist seeking to purify and use recombinant proteins. Reversible aggregation/precipitation induced by agents such as polyethylene glycol and salts can be used to purify proteins. However, proteins often undergo uncontrolled and irreversible aggregation that prevents regeneration of activity. This article summarizes methods to measure aggregation and to determine the intrinsic solubility of proteins. Much of this research has been driven by the need to formulate medically useful proteins so that they remain soluble, and to develop treatments for diseases that involve protein aggregation, such as Alzheimer's and other neurodegenerative diseases. Theoretical treatments of the effects of co‐solvents on the solubility of proteins, including using empirical data to derive atomic solvation parameters (ASP), may be useful for some applications. Mathematical models and protein phase diagrams have been developed for common precipitants, although there is no common basis for their a priori use with a given protein. There are also some general rules for designing mutants with reduced aggregation tendencies. To this end, computational methods may be used to estimate the solvent exposure of residues in 3D‐structures, predict surface patches that may dictate protein–protein interactions, and to model the 3D structure.

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A Model for the Prediction of Precipitation Curves for Globular Proteins with Nonionic Polymers as the Precipitating Agent

Cited by 6 publications

References 25 publications

Mechanism of Protein−Poly(ethylene glycol) Interaction from a Diffusive Point of View

Mechanism of Protein−Poly(ethylene glycol) Interaction from a Diffusive Point of View

Protein Aggregation, Denaturation

Protein Aggregation and Precipitation, Measurement and Control

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