A Pseudopolyrotaxane for Glucose-Responsive Insulin Release: The Effect of Binding Ability and Spatial Arrangement of Phenylboronic Acid Group

A pseudopolyrotaxane (PPRX) comprising 3-carboxy-5-nitrophenylboronic acid modified gamma-cyclodextrin (NPBA-gamma-CyD) and naphthalene modified polyethylene glycol (Naph-PEG) as a sugar responsive supramolecular structure is prepared. The binding of sugar by the NPBA group induced disintegration of the Naph-PEG/NPBA-gamma-CyD PPRX, allowing the components to be dissolved. The NaphPEG/NPBA-gamma-CyD PPRX exhibited better sensitivity compared to that of a PPRX based on 4-carboxyphenylboronic acid modified gamma-cyclodextrin (PBA-gamma-CyD). We have previously reported the unique structure of Naph-PEG/PBA-gamma-CyD PPRX, which formed an inclusion complex with a single-stranded PEG chain being threaded through the gamma-CyD rings, with the remaining internal space being occupied by the sugar-sensing PBA moiety from a neighboring ring, thus shielding it from sugar molecules and reducing the sugar sensitivity of the PPRX. In contrast, structural analyses in this study revealed that the sugar-sensing NPBA moiety in the Naph-PEG/NPBA-gamma-CyD PPRX is not included in the neighboring NPBA-gamma-CyD. This spatial arrangement and the high affinity of NPBA for sugar contributed to the improved sugar responsivity. The enhanced NPBA-gamma-CyD was then applied to a PPRX containing Naph-PEG-appended insulin (Naph-PEG-Ins) that showed an improved response for glucose-induced insulin release.