Surface molecular imprints of WGA lectin as artificial receptors for mass-sensitive binding studies

Wheat germ agglutinin (WGA) lectin is a model compound for the interaction between viruses and cells during infection events and thus an interesting analyte for mass-sensitive sensing to study these interaction phenomena. Scanning tunneling microscopy studies reveal that surface molecular imprinting leads to cavities having the dimensions of WGA dimers. These reincorporate WGA from phosphate-buffered saline between 1 and 160 μg/ml. Whereas the quartz crystal microbalance (QCM) frequency for molecularly imprinted polymer (MIP)-coated electrodes decreases, indicating uptake of the analyte, their nonimprinted counterparts yield positive, concentration-dependent frequency shifts characteristic for slip of the analyte on the QCM surface. The MIPs achieve selectivity factors towards bovine serum albumin of roughly 4 at higher protein concentrations. Brunauer-Emmett-Teller analysis reveals that binding is favored by 29 kJ/mol until the adsorption of up to ten monolayers on the MIP, whereas above this range the value is lower. Together with the binding behavior of MIP and nonimprinted polymers, this indicates that the MIP acts as a nucleus for multilayer deposition onto the surface.     

Identification of Vinyl Sulfone Derivatives as EGFR Tyrosine Kinase Inhibitor: In Vitro and In Silico Studies

Epidermal growth factor receptor (EGFR), overexpressed in many types of cancer, has been proved as a high potential target for targeted cancer therapy due to its role in regulating proliferation and survival of cancer cells. In the present study, a series of designed vinyl sulfone derivatives was screened against EGFR tyrosine kinase (EGFR-TK) using in silico and in vitro studies. The molecular docking results suggested that, among 78 vinyl sulfones, there were eight compounds that could interact well with the EGFR-TK at the ATP-binding site. Afterwards, these screened compounds were tested for the inhibitory activity towards EGFR-TK using ADP-Glo™ kinase assay, and we found that only VF16 compound exhibited promising inhibitory activity against EGFR-TK with the IC₅₀ value of 7.85 ± 0.88 nM. In addition, VF16 showed a high cytotoxicity with IC₅₀ values of 33.52 ± 2.57, 54.63 ± 0.09, and 30.38 ± 1.37 µM against the A431, A549, and H1975 cancer cell lines, respectively. From 500-ns MD simulation, the structural stability of VF16 in complex with EGFR-TK was quite stable, suggesting that this compound could be a novel small molecule inhibitor targeting EGFR-TK.