In vitro investigation of the binding characteristics of dacomitinib to human α 1-acid glycoprotein: Multispectral and computational modeling.

Dacomitinib is a highly selective second-generation tyrosine kinase inhibitor that can irreversibly bind to tyrosine kinase and is mainly used in the treatment of lung cancer. The binding characteristics of dacomitinib with human α 1-acid glycoprotein (HAG) were analyzed by multispectral and computational simulation techniques. The fluorescence spectra showed that dacomitinib can quench the fluorescence of HAG by forming the HAG-dacomitinib complex with a molar ratio of 1:1 (static quenching). At the temperature similar to that of the human body, the affinity of dacomitinib to HAG (8.95 × 106 M-1) was much greater than that to BSA (3.39 × 104 M-1), indicating that dacomitinib will give priority to binding onto HAG. Thermodynamics parameters analysis and driving force competition experiments showed that hydrogen bonding and hydrophobic forces were the major sources for keeping the complex of HAG-dacomitinib stable. The experimental outcomes also showed that the binding of dacomitinib can lead to the loosening of the skeleton structure of HAG, which led to a slight change in the secondary structure, and also reduces the hydrophobicity of the microenvironment of Trp and Tyr residues. The binding sites of dacomitinib on HAG and the contribution of key amino acid residues to the binding reaction were determined by molecular docking and molecular dynamics (MD) simulation. In addition, it was found that there was a synergistic effect between dacomitinib and Mg2+ and Co2+ ions. Mg2+ and Co2+ could increase the Kb of dacomitinib to HAG and prolong the half-life of dacomitinib.

Spherical porphyrin sensor array based on encoded colloidal crystal beads for VOC vapor detection.

A spherical porphyrin sensor array using colloidal crystal beads (CCBs) as the encoding microcarriers has been developed for VOC vapor detection. Six different porphyrins were coated onto the CCBs with distinctive encoded reflection peaks via physical adsorption and the sensor array was fabricated by placing the prepared porphyrin-modified CCBs together. The change in fluorescence color of the porphyrin-modified CCBs array serves as the detection signal for discriminating between different VOC vapors and the reflection peak of the CCBs serves as the encoding signal to distinguish between different sensors. It was demonstrated that the VOC vapors detection using the prepared sensor array showed excellent discrimination: not only could the compounds from the different chemical classes be easily differentiated (e.g., alcohol vs acids vs ketones) but similar compounds from the same chemical family (e.g., methanol vs ethanol) and the same compound with different concentration ((e.g., Sat. ethanol vs 60 ppm ethanol vs 10 ppm ethanol) could also be distinguished. The detection reproducibility and the humidity effect were also investigated. The present spherical sensor array, with its simple preparation, rapid response, high sensitivity, reproducibility, and humidity insensitivity, and especially with stable and high-throughput encoding, is promising for real applications in artificial olfactory systems.