title: A Pseudopolyrotaxane for Glucose-Responsive Insulin Release: The Effect of Binding Ability and Spatial Arrangement of Phenylboronic Acid Group.
abstract: A pseudopolyrotaxane (PPRX) comprising 3-carboxy-5-nitrophenylboronic acid modified γ-cyclodextrin (NPBA-γ-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-γ-CyD PPRX, allowing the components to be dissolved. The Naph-PEG/NPBA-γ-CyD PPRX exhibited better sensitivity compared to that of a PPRX based on 4-carboxyphenylboronic acid modified γ-cyclodextrin (PBA-γ-CyD). We have previously reported the unique structure of Naph-PEG/PBA-γ-CyD PPRX, which formed an inclusion complex with a single-stranded PEG chain being threaded through the γ-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-γ-CyD PPRX is not included in the neighboring NPBA-γ-CyD. This spatial arrangement and the high affinity of NPBA for sugar contributed to the improved sugar responsivity. The enhanced NPBA-γ-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.
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University , Keyakidai, Sakado, Saitama 350-0295, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Seki
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University , Keyakidai, Sakado, Saitama 350-0295, Japan.
authors.forename: Keigo
authors.initials: K
authors.lastname: Abe
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University , Keyakidai, Sakado, Saitama 350-0295, Japan.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Egawa
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University , Keyakidai, Sakado, Saitama 350-0295, Japan.
authors.forename: Ryotaro
authors.initials: R
authors.lastname: Miki
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University , Keyakidai, Sakado, Saitama 350-0295, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Juni
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University , Keyakidai, Sakado, Saitama 350-0295, Japan.
authors.forename: Toshinobu
authors.initials: T
authors.lastname: Seki
mesh_terms: D001897:Boronic Acids / Q000737:chemistry*; D003505:Cyclodextrins / Q000737:chemistry*; D005947:Glucose / Q000737:chemistry*; D007328:Insulin / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D009281:Naphthalenes / Q000737:chemistry; D020442:Poloxamer / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D043862:Rotaxanes / Q000737:chemistry*
chemical_list: D001897:Boronic Acids; D003505:Cyclodextrins; D007328:Insulin; D009281:Naphthalenes; D043862:Rotaxanes; C475674:pseudopolyrotaxane; D020442:Poloxamer; C031721:naphthalene; D011092:Polyethylene Glycols; D005947:Glucose; C010686:benzeneboronic acid
keywords: boronic acid; cyclodextrin; insulin; polypseudorotaxane; pseudopolyrotaxane; stimulus-responsive