Hydrogen Peroxide-Triggered Conversion of Boronic Acid-Appended Insulin into Insulin and Its Application as a Glucose-Responsive Insulin Formulation
| Autor: | Miho Koita, Yuya Egawa, Yuki Nakamura, Hiroki Koyama, Minori Kojima, Hinako Kikuchi, Toshinobu Seki, Chika Inoue, Ryotaro Miki, Sayaka Nojiri |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Blood Glucose
insulin boronic acid medicine.medical_treatment Injections Subcutaneous Pharmaceutical Science Endogeny macromolecular substances Hypoglycemia Glucose responsive chemistry.chemical_compound Glucose Oxidase Insulin Regular Human Drug Discovery medicine Animals Humans 血糖値応答性 Protecting group Hydrogen peroxide Oxidase test Chemistry 低血糖 Insulin glucose-responsive release Hydrogen Peroxide medicine.disease Boronic Acids Rats インスリン carbohydrates (lipids) Disease Models Animal Drug Liberation hypoglycemia Biochemistry Diabetes Mellitus Type 2 Delayed-Action Preparations 過酸化水素 Molecular Medicine lipids (amino acids peptides and proteins) ボロン酸 Oxidation-Reduction Boronic acid |
| Zdroj: | Molecular pharmaceutics. 18(11) |
| ISSN: | 1543-8392 |
| Popis: | p-Boronophenylmethoxycarbonyl (BPmoc) is a protecting group for amines that is 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 that BPmoc effectively sealed the blood glucose (Glc)-lowering effects of Ins. Conversely, coinjection of BPmoc-Ins and Glc oxidase (GOx) resulted in reduced blood Glc levels, indicating that Ins was generated from BPmoc-Ins through the following reactions: oxidation of endogenous Glc by GOx; production of H2O2 accompanied by Glc oxidation; removal of BPmoc residues by H2O2. These results show the potential of BPmoc-Ins for a Glc-responsive Ins release system. |
| Databáze: | OpenAIRE |
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