Abiotic Mimic of Endogenous Tissue Inhibitors of Metalloproteinases: Engineering Synthetic Polymer Nanoparticles for Use as a Broad-Spectrum Metalloproteinase Inhibitor
| Autor: | Masahiko Nakamoto, Di Zhao, Kenneth J. Shea, Shih-Hui Lee, Olivia Rose Benice |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Polymers
Nanoparticle Endogeny Matrix metalloproteinase 010402 general chemistry 01 natural sciences Biochemistry Catalysis Colloid and Surface Chemistry Biomimetics medicine Abiotic component chemistry.chemical_classification Tissue Inhibitor of Metalloproteinases General Chemistry Polymer 0104 chemical sciences Zinc Enzyme Mechanism of action chemistry Snake venom Metalloproteases Nanoparticles medicine.symptom |
| Zdroj: | Journal of the American Chemical Society. 142:2338-2345 |
| ISSN: | 1520-5126 0002-7863 |
| DOI: | 10.1021/jacs.9b11481 |
| Popis: | We describe a process for engineering a synthetic polymer nanoparticle (NP) that functions as an effective, broad-spectrum metalloproteinase inhibitor. Inhibition is achieved by incorporating three functional elements in the NP: a group that interacts with the catalytic zinc ion, functionality that enhances affinity to the substrate-binding pocket, and fine-tuning of the chemical composition of the polymer to strengthen NP affinity for the enzyme surface. The approach is validated by synthesis of a NP that sequesters and inhibits the proteolytic activity of snake venom metalloproteinases from five clinically relevant species of snakes. The mechanism of action of the NP mimics that of endogenous tissue inhibitors of metalloproteinases. The strategy provides a general design principle for synthesizing abiotic polymer inhibitors of enzymes. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|