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

• DOI: 10.1021/acs.molpharmaceut.6b00599
• Publication Date: 2016-10-07T18:08:10Z
• Authors: Tomohiro Seki; Keigo Abe; Yuya Egawa; Ryotaro Miki; Kazuhiko Juni; Toshinobu Seki
• Keywords: Phenylboronic acid; Moiety

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