Screening and investigation of triplex DNA binders from Stephania tetrandra S. Moore by a combination of peak area-fading ultra high-performance liquid chromatography with orbitrap mass spectrometry and optical spectroscopies

Journal of Separation Science
Hongmei YangShuying Liu

Abstract

The identification and screening of triplex DNA binders are important because these compounds, in many cases, are potential anticancer agents as well as promising drug candidates. Therefore, the ability to screen for these compounds in a high-throughput mode could dramatically improve the drug screening process. A method involving a combination of 96-well plate format and peak area-fading ultra high-performance liquid chromatography coupled with Orbitrap mass spectrometry was employed for screening bioactive compounds binding to the triplex DNA from the extracts of Stephania tetrandra S. Moore. Two compounds were screened out and identified as fangchinoline and tetrandrine based on the comparison of retention time and tandem mass spectrometry data with those of standards. The binding mechanisms of fangchinoline and tetrandrine at the molecular level were explored using tandem mass spectrometry, fluorescence spectroscopy, ultraviolet-visible spectroscopy, and circular dichroism. Collision-induced dissociation experiments showed that the complexes with fangchinoline and tetrandrine were dissociated by ligand elimination. According to these measurements, an intercalating binding is the most appropriate binding mode of these two al...Continue Reading

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Citations

Sep 7, 2019·Biochimica Et Biophysica Acta. Molecular Cell Research·Imee M A Del MundoGuliang Wang

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