Water-soluble, stable helical polypeptide-grafted cyclodextrinbioconjugates: synthesis, secondary and self-assembly structures, and inclusion complex with guest compounds

Abstract

In this study, we synthesized a linear copolymer, poly(γ-propargyl-L-glutamate-graft-cyclodextrin) (PPLG-g-CD), through Huisgen [2 + 3] cycloadditions (click reactions) of monoazido-functionalized β-cyclodextrin (N₃-CD) with the propargyl side chains, obtaining a self-assembling structure with a highly stable α-helical conformation and water-solubility. We used Fourier transform infrared spectroscopy, solid state nuclear magnetic resonance spectroscopy, wide-angle X-ray diffraction, and circular dichroism analyses in the solid state and in solution to characterize the transformations of the secondary structures between α-helix and β-sheet conformations. Temperature-dependent FTIR spectroscopic analyses revealed that the presence of the CD units on the PPLG side chain increased the stability of the α-helix conformation toward elevated temperatures, relative to that of pure PPLG. In addition, the presence of the CD cavities allowed the grafted polymers to form inclusion complexes with low-molecular-weight compounds, providing macromolecules with potential biomedical applications.