RESUMEN
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.
Asunto(s)
Biomimética , Metaloproteasas/antagonistas & inhibidores , Nanopartículas/química , Polímeros/química , Inhibidores Tisulares de Metaloproteinasas/farmacología , Catálisis , Zinc/químicaRESUMEN
In this work, we report on a rapid, efficient electrochemical iodine sensor based on mechanically treated carbon nanofiber (MCNF) electrodes. The electrode’s highly graphitic content, unique microstructure, and the presence of nitrogen heteroatoms in its atomic lattice contribute to increased heterogeneous electron transfer and improved kinetics compared to conventional pyrolytic carbons. The electrode demonstrates selectivity for iodide ions in the presence of both interfering agents and high salt concentrations. The sensor exhibits clinically relevant limits of detection of 0.59 µM and 1.41 µM, in 1X PBS and synthetic urine, respectively, and a wide dynamic range between 5 µM and 700 µM. These results illustrate the advantages of the material’s unique electrochemical properties for iodide sensing, in addition to its simple, inexpensive fabrication. The reported iodine sensor eliminates the need for specimen processing, revealing its aptitude for applications in point-of-care diagnostics.