Stabilization of protein structure by sugars

Arakawa, Tsutomu; Timasheff, Serge N.

doi:10.1021/bi00268a033

Cited by 1,050 publications

(716 citation statements)

References 38 publications

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“…This should have as consequences a reduction of the exclusion and a less positive perturbation of the PEG chemical potential by the protein, just as is observed. This effect of pH on the preferential interactions is strikingly opposite to the effect of glucose on the preferential hydrations of BSA at pH 3.0 and 6.0 (Arakawa & Timasheff, 1982a). Contrary to the current observations with the PEGs, for the sugar solution system the hydration is larger at the lower pH.…”

Section: As Well As the Appendix Of Arakawa Et Al (1990a)contrasting

confidence: 99%

Steric exclusion is the principal source of the preferential hydration of proteins in the presence of polyethylene glycols

1992

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The preferential interactions of bovine serum albumin, lysozyme, chymotrypsinogen, ribonuclease A, and 6-lactoglobulin with polyethylene glycols (PEGS) of molecular weight 200-6,OOO have been measured by dialysis equilibrium coupled with high precision densimetry. All the proteins were found to be preferentially hydrated in all the PEGs, and the magnitude of the preferential hydration increased with increasing PEG size for each protein.The change in the chemical potentials of the proteins with the addition of the PEGs had highly positive values, indicating a strong thermodynamic destabilization of the system by the PEGs. A viscosity study of the PEGs showed them to be randomly coiled polymers, as their radii of gyration were related to the molecular weight by R, = a M 0 , 5 s . The thickness of the effective shell impenetrable to PEG around protein molecules, calculated from the preferential hydration, was found to vary with PEG molecular weight in similar fashion as the PEG radius of gyration, supporting the proposal (Arakawa, T. & Timasheff, S.N., 1985a, Biochemistry 24,6756-6762) that the preferential exclusion of PEGs from proteins is due principally to the steric exclusion of PEG from the protein domain, although favorable interactions with protein surface residues, in particular nonpolar ones, may compete with the exclusion. These thermodynamically unfavorable preferential exclusion interactions lead to the action of PEGs as precipitants, although they may destabilize protein structure at higher temperatures.

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Section: As Well As the Appendix Of Arakawa Et Al (1990a)contrasting

confidence: 99%

Steric exclusion is the principal source of the preferential hydration of proteins in the presence of polyethylene glycols

1992

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“…This is done by multiplying the calculated value of (apz/am3);,,,, by the ratio, R , of the experimental to the calculated value determined for systems that show no evidence of binding. In previous studies, it has been shown that R has values between 0.5 and 0.7 (Arakawa & Timasheff, 1982a, 1983, 1984b, which are similar to those calculated by Honig and co-workers from geometric considerations Sharp et al, 1991). Therefore, for consistency, all the preferential interaction parameters calculated with the Gibbs adsorption isotherm were corrected by this factor.…”

Section: Separation Of the Measured Preferential Exclusion Into Contrsupporting

confidence: 58%

“…RNaseA was further purified on a sulfoethyl-Sephadex C25 column, according to Crestfield et al (1962). The protein was deionized exhaustively by dialyzing against doubly distilled water or passing through a mixed-bed ion exchange resin (Amberlite MB-1) and finally lyophilized (Gekko & Timasheff, 1981;Arakawa & Timasheff, 1982a).…”

Section: Methodsmentioning

confidence: 99%

“…In other words, the preferential interaction, expressed as preferential binding of co-solvent, will assume positive or negative values in the two respective cases. In dialysis equilibrium experiments, it has been found that sugars, amino acids, and many salts are preferentially excluded from the protein surface, i.e., their preferential interactions with proteins are negative (Lee & Timasheff, 1981;Arakawa & Timasheff, 1982a, 1982b, 1983Kita et al, 1994). All of these co-solvents raise the surface tension of water.…”

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confidence: 99%

“…All of these co-solvents raise the surface tension of water. The good correlation between the measured negative preferential interactions and the positive surface tension increment in their presence (Arakawa & Timasheff, 1982a, 1982b, 1983, 1984bKita et al, 1994) led to the proposal that this is the principal source of the unfavorable free energy of the interactions of these co-solvents with proteins. These observations have suggested that the stabilization of proteins by these co-solvents is due to the increase of the surface tension in their presence.…”

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confidence: 99%

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On the role of surface tension in the stabilization of globular proteins

1996

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The stabilization of proteins by a variety of co-solvents can be related to their property of increasing the surface tension of water. It is demonstrated that, during the thermal unfolding of proteins, this increase of the surface tension can be overcome by the increase in the temperature of the solution at the midpoint of the transition, T,, and the weak binding of co-solvent molecules. Three such co-solvents were studied: trehalose, lysine hydrochloride (LysHCl), and arginine hydrochloride (ArgHC1). Trehalose and LysHCl increase the midpoint of T,. The increase of the surface tension by addition of trehalose is completely compensated by its decrease due to the increase in T,. However, for LysHC1, the increase of the surface tension by the co-solvent is partly reduced by its binding to the protein. Later studies on the preferential interaction2 of proteins with a variety of co-solvents have identified the surface tension ef-'The term preferential interaction refers to the net interaction between the protein and the solvent components, water and the co-solvent, as measured by an equilibrium thermodynamic approach, such as dialysis equilibrium. When the interactions are weak, as is the case with co-solvents, such as sugars, glycerol, amino acids, or urea, the measured quantity is the net balance between the weak interactions (binding) of water and co-solvent molecules to the protein over its entire surface. If, on average, the affinity of protein surface loci for the co-solvent is greater than that for water, the dialysis equilibrium experiment will result in an excess of co-solvent at the protein surface over its concentration in the bulk solvent, and the measured binding stoichiometry will be positive, which means that co-solvent is preferentially bound relative to water. In that case, the "preferential binding" will be positive. In the converse case, in which, on average, the affinity of the protein surface loci is greater for water than for co-solvent molecules, there will be an excess of water at the protein surface over its concentration in the 372

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Secondary structure changes and peptic hydrolysis of β-lactoglobulin induced by diols

et al. 1998

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The addition of ethylene glycol, and 1,2‐ and 1,3‐propanediol, decreases the bulk dielectric constant of the medium, and according to CD measurements, increases significantly the proportion of helical structure in β‐lactoglobulin. The medium‐induced folding changes followed by limited peptic hydrolysis show that the cleavage of β‐lactoglobulin by pepsin is triggered by structural transformations induced by ethylene glycol only and not by 1,2‐ and 1,3‐propanediol. Density measurements, at constant chemical potential and constant molality, demonstrate that all diols are present in the immediate domain of the protein. They are engaged in hydrophobic interactions with the amino acids of β‐lactoglobulin core inducing the formation of additional α‐helices. © 1996 John Wiley & Sons, Inc.

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Stabilization of protein structure by sugars

Cited by 1,050 publications

References 38 publications

Steric exclusion is the principal source of the preferential hydration of proteins in the presence of polyethylene glycols

Steric exclusion is the principal source of the preferential hydration of proteins in the presence of polyethylene glycols

On the role of surface tension in the stabilization of globular proteins

Secondary structure changes and peptic hydrolysis of β-lactoglobulin induced by diols

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