Electrochemical Immunosensor Using <i>p</i>-Aminophenol Redox Cycling by Hydrazine Combined with a Low Background Current

Signal amplification and noise reduction are crucial for obtaining low detection limits in biosensors. Here, we present an electrochemical immunosensor in which the signal amplification is achieved using p-aminophenol (AP) redox cycling by hydrazine, and the noise level is reduced by implementing a low background current. The redox cycling is obtained in a simple one-electrode, one-enzyme format. In a sandwich-type heterogeneous immunosensor for mouse IgG, an alkaline phosphatase label converts p-aminophenyl phosphate into AP for 10 min. This generated AP is electrooxidized at an indium tin oxide (ITO) electrode modified with a partially ferrocenyl-tethered dendrimer (Fc-D). The oxidized product, p-quinone imine (QI), is reduced back to AP by hydrazine, and then AP is electrooxidized again to QI, resulting in redox cycling. Moreover, hydrazine protects AP from oxidation by air, enabling long incubation times. The small amount of ferrocene in a 0.5% Fc-D-modified ITO electrode, where 0.5% represents the ratio of ferrocene groups to dendrimer amines, results in a low background current, and this electrode exhibits high electron-mediating activity for AP oxidation. Moreover, there is insignificant hydrazine electrooxidation on this electrode, which also results in a low background current. The detection limit of the immunosensor using a 0.5% Fc-D-modified electrode is 2 orders of magnitude lower than that of a 20% Fc-D-modified electrode (10 pg/mL vs 1 ng/mL). Furthermore, the presence of hydrazine reduces the detection limit by an additional 2 orders of magnitude (100 fg/mL vs 10 pg/mL). These results indicate that the occurrence of redox cycling combined with a low background current yields an electrochemical immunosensor with a very low detection limit (100 fg/mL). Mouse IgG could be detected at concentrations ranging from 100 fg/mL to 100 μg/mL (i.e., 9 orders of magnitude) in a single assay

Additional file 1 of Iterative machine learning-based chemical similarity search to identify novel chemical inhibitors

Additional file 1: Figure S1. The duplicated dose response curves to determine Kd values of chemical compounds are shown for MEK1, MEK2, and MEK5. X-axis represents ligand concentration (nM) and Y-axis relative inhibitory activity by KdELECT service. Figure S2. Structurally similar molecules were identified via substructure search in Reaxys database. Figure S3. Molecular docking conformations of ZINC5814210 for MEK1, MEK2, and MEK5 are superimposed with ATP found in the MEK1 structure (PDB ID: 3V01). Figure S4. Two-dimensional interaction diagram of previously reported MEK1 inhibitors retrieved by 2D fingerprint similarity. Figure S5. Two-dimensional interaction diagram of MEK-ZINC5479148 docking models. Figure S6. Two-dimensional interaction diagram of MEK-ZINC32911363 docking models. Except MEK2, ZINC32911363 has better Kd binding affinity to other two MEKs. Figure S7. The molecules selected based on binding free energy scores from either MM/GBSA or MM/PBSA or both of the methods. Table S1. Experimental chemical activity data and cross-validation results (AUC of Precision-Recall curve) for each test target protein. Table S2. Comparison of the prediction performance of the standard single chemical-based Random Forest model with the ECBS model trained with PP-NP-NN data. Table S3. Estimation of chemical pair data size. Table S4. LogP values for the tested compounds. Table S5. GNINA docking scores for MEKs are shown with biochemical binding affinity data in Table 3. Table S6. The target prediction results for ZINC5814210 from Swiss target prediction server. Table S7. The target prediction results for ZINC5814210 from Structure Ensemble Approach (SEA) server

Additional file 2 of Iterative machine learning-based chemical similarity search to identify novel chemical inhibitors

Additional file 2: Table S1. SMILES for the tested compounds

Facile Approach for Diblock Codendrimers by Fusion between Fréchet Dendrons and PAMAM Dendrons

For the first time, a simple and facile approach for the synthesis of diblock codendrimers by fusion between the azide focal point functionalized Fréchet-type polyether and the propargyl focal point functionalized Tomalia-type PAMAM dendrons has been described based on click chemistry, i.e., the copper-catalyzed cycloaddition reaction between alkyne and azide

Patient characteristics in all patients.

Patient characteristics in all patients.</p

Thiiranes: Intelligent Molecules for S‑Persulfidation

This study presents a global strategy for the transsulfuration of intracellular thiols (RSH) to persulfides (RSSH). Thiiranes comprising fluorenyl/diphenyl and malonate ester moieties directly convert intercellular RSH to low-molecular-weight RSSH in cells. The efficiency of transsulfuration is determined by counting the number of olefins produced as byproducts, providing ratiometric signals for the corresponding persulfide production. Specifically, the direct and rapid protein S-persulfidation by thiirane is validated. Thiiranes are expected to play a crucial role in the study of sulfur signaling

Combinatorial Approach to Organelle-Targeted Fluorescent Library Based on the Styryl Scaffold

The first fluorescent styryl dye library with a broad color range was synthesized by combinatorial condensation of various aldehydes and methyl pyridinium compounds, and their applications as organelle specific staining probes were demonstrated

Multivariate logistic regression of LDIs for diagnosis BO.

Multivariate logistic regression of LDIs for diagnosis BO.</p

Univariate and multivariate linear regression for lung density indices (LDIs) with conventional PFTs.

Univariate and multivariate linear regression for lung density indices (LDIs) with conventional PFTs.</p

Comparison of quantitative lung densitometry indices and conventional pulmonary function test results according to diagnosis.

Comparison of quantitative lung densitometry indices and conventional pulmonary function test results according to diagnosis.</p