Alpha-beta transition induced by C18-conjugation of polyalanine and its implication in aqueous solution behavior of poly(ethylene glycol)-polyalanine block copolymers

Abstract

BackgroundThe aqueous solution behavior of thermosensitive PEG-PA block copolymers as well as secondary structure of PA is expected to significantly change through modification of the hydrophobic PA by long chain alkyl (C18) groups with different configurations.MethodOleoyl and stearoyl (C18) groups were conjugated to poly(ethylene glycol)-poly(L-alanine) (PEG-PA; EG(45)A(16)) diblock copolymers to compare their conjugation effect on nano-assemblies and corresponding aqueous solution behavior of the polymers.ResultsDue to the nature of a hydrophilic PEG block and a hydrophobic PA or C18-modified PA, PEG-PA, oleoyl group-conjugated PEG-PA (PEG-PAO), and stearoyl group-conjugated PEG-PA (PEG-PAS) block copolymers form micelles in water. Compared with PEG-PA, the micelle size of PEG-PAO and PEG-PAS increased. Circular dichroism and FTIR spectra of aqueous polymer solutions showed that beta sheet content increased, whereas alpha helix content decreased by C18 modification of PEG-PA. PEG-PAS showed better performance in ice crystallization inhibition than PEG-PAO. The sol-to-gel transition temperatures of aqueous PEG-PAO solutions were 25-37 degrees C higher than those of aqueous PEG-PA solutions, whereas aqueous PEG-PAS solutions remained as gels in the temperature range of 0-80 degrees C. H-1-NMR spectra indicated that the oleoyl groups increased core mobility, whereas stearoyl groups decreased the core mobility of the micelles in water. The difference in micromobility between PAO and PAS interfered or promoted gelation of the aqueous polymer solutions, respectively.ConclusionsThis study suggests that a hydrophobic C18-modification of polypeptide induces alpha helix-to-beta sheet transition of the polypeptide; however, aqueous solution behaviors including ice recrystallization inhibition and gelation are significantly affected by the nature of the hydrophobic molecule.