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Selective Syntheses of Unsymmetrical Diaryl Sulfides Enabled by a Sulfur Dioxide Surrogate as a Divalent Sulfur Source and an Activating Agent
No full textapplication/pdfOrganic sulfides are prevalent in nature and artificially synthesized molecules, including pharmaceuticals, agrochemicals, and functional materials. However, existing methods of synthesizing organic sulfides have limitations, such as the use of unstable, prefunctionalized sulfur sources and the need for additional synthetic steps. While effective for symmetrical and cyclic sulfides, few methods have been reported for synthesizing simple unsymmetrical sulfides via single three-component reactions. Therefore, in this study, a highly selective general method of synthesizing unsymmetrical diaryl sulfides, enabled by a Cu catalyst and potassium metabisulfite (K2S2O5), which is a sulfur dioxide (SO2) surrogate, is established. The three-component synthetic method offers safe, convenient access to unsymmetrical sulfides without using hazardous SO2 gas and preformed C–S bond-containing compounds such as thiols and disulfides. The detailed reaction mechanism supported by theoretical calculations is analyzed, indicating the roles of SO2 as a divalent S source as well as an activating agent for deoxygenation at the S atom.journal articl
Development of a mertansine-specific DNA aptamer and novel high-throughput sandwich enzyme-linked oligonucleotide assay for quantification and characterization of trastuzumab emtansine
Get PDFapplication/pdfWe developed a novel DNA aptamer, D8#24S1, which specifically recognizes mertansine (DM1), the cytotoxic payload of the antibody-drug conjugate (ADC) trastuzumab emtansine (T-DM1), and applied it for T-DM1 analysis. D8#24S1 was obtained through SELEX and was shown to specifically recognize DM1 with high affinity (dissociation constant, KD =84.2 nM). By combining this anti-payload aptamer with the trastuzumab-specific anti-idiotype aptamer, CH1-S3, we developed a sandwich enzyme-linked oligonucleotide assay (sELONA) for evaluating T-DM1 content and drug-to-antibody ratio (DAR). The sELONA demonstrated an excellent fit to 4- parameter logistic curve model (R2 =0.994) over a T-DM1 concentration range of 1–500 μg/mL, with a lower limit of quantification of 1 μg/mL, a precision within 23.9% (n =3), and an accuracy within ±20.2% (n = 3). The sELONA also showed specificity when tested with other therapeutic monoclonal antibodies, such as trastuzumab and bevacizumab, as well as complex samples like serum. For DAR analysis, the sELONA exhibited high linearity (R2 =0.988) and a strong correlation with hydrophobic interaction chromatography, a conventional method (R2 =0.984). Unlike antibody-based assays, such as enzyme-linked immunosorbent assays, the sELONA employs chemically synthesized aptamers, offering superior robustness and cost-effectiveness. Additionally, when compared to conventional HIC, sELONA utilizes a 96-well microplate format, enabling high- throughput analysis. This study demonstrates the feasibility of aptamer-based assays as reliable alternatives to antibody-dependent methods, providing an efficient and adaptable approach for evaluating ADCs and potentially contributing to streamlined pharmaceutical development.journal articl
