title: Chemical Interactions of Polyethylene Glycols (PEGs) and Glycerol with Protein Functional Groups: Applications to Effects of PEG and Glycerol on Protein Processes.
abstract: In this work, we obtain the data needed to predict chemical interactions of polyethylene glycols (PEGs) and glycerol with proteins and related organic compounds and thereby interpret or predict chemical effects of PEGs on protein processes. To accomplish this, we determine interactions of glycerol and tetraEG with >30 model compounds displaying the major C, N, and O functional groups of proteins. Analysis of these data yields coefficients (α values) that quantify interactions of glycerol, tetraEG, and PEG end (-CH2OH) and interior (-CH2OCH2-) groups with these groups, relative to interactions with water. TetraEG (strongly) and glycerol (weakly) interact favorably with aromatic C, amide N, and cationic N, but unfavorably with amide O, carboxylate O, and salt ions. Strongly unfavorable O and salt anion interactions help make both small and large PEGs effective protein precipitants. Interactions of tetraEG and PEG interior groups with aliphatic C are quite favorable, while interactions of glycerol and PEG end groups with aliphatic C are not. Hence, tetraEG and PEG300 favor unfolding of the DNA-binding domain of lac repressor (lacDBD), while glycerol and di- and monoethylene glycol are stabilizers. Favorable interactions with aromatic and aliphatic C explain why PEG400 greatly increases the solubility of aromatic hydrocarbons and steroids. PEG400-steroid interactions are unusually favorable, presumably because of simultaneous interactions of multiple PEG interior groups with the fused ring system of the steroid. Using α values reported here, chemical contributions to PEG m-values can be predicted or interpreted in terms of changes in water-accessible surface area (ΔASA) and separated from excluded volume effects.
authors.affiliation: †Department of Biochemistry, ‡Department of Chemistry, and §Program in Biophysics, University of Wisconsin-Madison, 433 Babcock Drive, Madison, Wisconsin 53706, United States.
authors.forename: D B
authors.initials: DB
authors.lastname: Knowles
authors.affiliation: †Department of Biochemistry, ‡Department of Chemistry, and §Program in Biophysics, University of Wisconsin-Madison, 433 Babcock Drive, Madison, Wisconsin 53706, United States.
authors.forename: Irina A
authors.initials: IA
authors.lastname: Shkel
authors.affiliation: †Department of Biochemistry, ‡Department of Chemistry, and §Program in Biophysics, University of Wisconsin-Madison, 433 Babcock Drive, Madison, Wisconsin 53706, United States.
authors.forename: Noel M
authors.initials: NM
authors.lastname: Phan
authors.affiliation: †Department of Biochemistry, ‡Department of Chemistry, and §Program in Biophysics, University of Wisconsin-Madison, 433 Babcock Drive, Madison, Wisconsin 53706, United States.
authors.forename: Matt
authors.initials: M
authors.lastname: Sternke
authors.affiliation: †Department of Biochemistry, ‡Department of Chemistry, and §Program in Biophysics, University of Wisconsin-Madison, 433 Babcock Drive, Madison, Wisconsin 53706, United States.
authors.forename: Emily
authors.initials: E
authors.lastname: Lingeman
authors.affiliation: †Department of Biochemistry, ‡Department of Chemistry, and §Program in Biophysics, University of Wisconsin-Madison, 433 Babcock Drive, Madison, Wisconsin 53706, United States.
authors.forename: Xian
authors.initials: X
authors.lastname: Cheng
authors.affiliation: †Department of Biochemistry, ‡Department of Chemistry, and §Program in Biophysics, University of Wisconsin-Madison, 433 Babcock Drive, Madison, Wisconsin 53706, United States.
authors.forename: Lixue
authors.initials: L
authors.lastname: Cheng
authors.affiliation: †Department of Biochemistry, ‡Department of Chemistry, and §Program in Biophysics, University of Wisconsin-Madison, 433 Babcock Drive, Madison, Wisconsin 53706, United States.
authors.forename: Kevin
authors.initials: K
authors.lastname: O'Connor
authors.affiliation: †Department of Biochemistry, ‡Department of Chemistry, and §Program in Biophysics, University of Wisconsin-Madison, 433 Babcock Drive, Madison, Wisconsin 53706, United States.
authors.forename: M Thomas
authors.initials: MT
authors.lastname: Record
mesh_terms: D029968:Escherichia coli Proteins / Q000737:chemistry*; D005990:Glycerol / Q000737:chemistry*; D056968:Lac Repressors / Q000737:chemistry*; D008956:Models, Chemical; D011092:Polyethylene Glycols / Q000737:chemistry*
chemical_list: D029968:Escherichia coli Proteins; D056968:Lac Repressors; C539064:LacI protein, E coli; D011092:Polyethylene Glycols; D005990:Glycerol