The role of polymer size and hydrophobic end-group in PEG–protein interaction

• PEG binds BSA and HSA via hydrophobic and H-bonding contacts.
• PEG forms more stable complexes with HSA than BSA.
• Increasing PEG molecular weight improves the stability of polymer–protein complexes.
• mPEG-anthracene forms stronger complexes with BSA than HSA.
• Bindings of PEG and its anthracene derivative lead to a partial protein destabilization.

We investigated the interaction between polyethylene (glycol) (PEG) and human (HSA) and bovine serum albumin (BSA) in aqueous solution, using multiple spectroscopic methods and molecular modeling. The two important polymer characteristics, size and PEG hydrophobic end-group are studied in order to determine the effect of each one on PEG–protein interaction. The bindings of PEG and mPEG-anthracene with serum albumins occur via hydrophobic and H-bonding contacts with the binding affinity PEG-6000 > mPEG-anthracene > PEG-3000 for BSA and EG-6000 > PEG-3000 > mPEG-anthracene for HSA. Modeling showed different protein binding sites are involved in PEG–BSA and PEG–HSA complexes. Several H-bonding systems between PEG and different amino acids are stabilizing polymer–protein complexes. The free binding energies of −6.48 (PEG–BSA) and −6.36 kcal/mol (PEG–HSA) showed that the interaction process is spontaneous at room temperature. Minor alterations of protein alpha-helix and beta-sheet structures were observed upon PEG complexation.

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