Separating chemical and excluded volume interactions of polyethylene glycols with native proteins: Comparison with PEG effects on DNA helix formation.

ABSTRACT: Small and large PEGs greatly increase chemical potentials of globular proteins (?2), thereby favoring precipitation, crystallization, and protein-protein interactions that reduce water-accessible protein surface and/or protein-PEG excluded volume. To determine individual contributions of PEG-protein chemical and excluded volume interactions to ?2 as functions of PEG molality m3 , we analyze published chemical potential increments ?23 ?=?d?2/dm3 quantifying unfavorable interactions of PEG (PEG200-PEG6000) with BSA and lysozyme. For both proteins, ?23 increases approximately linearly with the number of PEG residues (N3). A 1 molal increase in concentration of PEG -CH2 OCH2 - groups, for any chain-length PEG, increases ?BSA by ?2.7 kcal/mol and ?lysozyme by ?1.0 kcal/mol. These values are similar to predicted chemical interactions of PEG -CH2 OCH2 - groups with these protein components (BSA ?3.3 kcal/mol, lysozyme ?0.7 kcal/mol), dominated by unfavorable interactions with amide and carboxylate oxygens and counterions. While these chemical effects should be dominant for small PEGs, larger PEGS are expected to exhibit unfavorable excluded volume interactions and reduced chemical interactions because of shielding of PEG residues in PEG flexible coils. We deduce that these excluded volume and chemical shielding contributions largely compensate, explaining why the dependence of ?23 on N3 is similar for both small and large PEGs.

SUBMITTER: Shkel IA 

PROVIDER: S-EPMC4485569 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature