Hydrogen Peroxide-Triggered Conversion of Boronic Acid-Appended Insulin into Insulin and Its Application as a Glucose-Responsive Insulin Formulation

• DOI: 10.1021/acs.molpharmaceut.1c00760
• Publication Date: 2021-10-09T06:57:26Z
• Authors: Hinako Kikuchi; Yuki Nakamura; Chika Inoue; Sayaka Nojiri; Miho Koita; Minori Kojima; Hiroki Koyama; Ryotaro Miki; Toshinobu Seki; Yuya Egawa
• Keywords: Glucose oxidase; Boronic acid; Peroxide

p-Boronophenylmethoxycarbonyl (BPmoc) is a protecting group for amines that removable by treatment with hydrogen peroxide (H2O2). We prepared BPmoc-modified insulin (BPmoc-Ins) and subcutaneously injected the formulation into diabetic rats. The results demonstrated BPmoc effectively sealed blood glucose (Glc)-lowering effects of Ins. Conversely, coinjection BPmoc-Ins Glc oxidase (GOx) resulted in reduced levels, indicating Ins was generated from through following reactions: oxidation endogenous GOx; production H2O2 accompanied oxidation; removal residues H2O2. These show potential Glc-responsive release system.