Mechanism of poly(ethylene glycol) interaction with proteins.
Poly(ethylene glycol) (PEG) is one of the most useful protein salting-out agents. In this study, it has been shown that the salting-out effectiveness of PEG can be explained by the large unfavorable free energy of its interaction with proteins. Preferential interaction measurements of beta-lactoglobulin with poly(ethylene glycols) with molecular weights between 200 and 1000 showed preferential hydration of the protein for those with Mr greater than or equal to 400, the degree of hydration increasing with the increase in poly(ethylene glycol) molecular weight. The preferential interaction parameter had a strong cosolvent concentration dependence, with poly(ethylene glycol) 1000 having the sharpest decrease with an increase in concentration. The preferential hydration extrapolated to zero cosolvent concentration increased almost linearly with increasing size of the additive, suggesting steric exclusion as the major factor responsible for the preferential hydration. The poly(ethylene glycol) concentration dependence of the preferential interactions could be explained in terms of the nonideality of poly(ethylene glycol) solutions. All the poly(ethylene glycols) studied, when used at levels of 10-30%, decreased the thermal stability of beta-lactoglobulin, suggesting that caution must be exercised in the use of this additive at extreme conditions such as high temperature.
D019791:Guanidine; D006146:Guanidines; D007782:Lactoglobulins; D008970:Molecular Weight; D011092:Polyethylene Glycols; D011489:Protein Denaturation; D011506:Proteins; D012259:Ribonuclease, Pancreatic; D013329:Structure-Activity Relationship; D013816:Thermodynamics
D006146:Guanidines; D007782:Lactoglobulins; D011506:Proteins; D011092:Polyethylene Glycols; D012259:Ribonuclease, Pancreatic; D019791:Guanidine