[Show abstract][Hide abstract] ABSTRACT: In this study, electrospray ionization mass spectrometry (ESI‐MS) was used to investigate interaction of 21 flavonoids (10 aglycones and 11 glycosides) with the parallel quadruplex structure [d(TGGGGT)]4. Relative binding affinities of flavonoids toward [d(TGGGGT)]4 were estimated based on the fraction of bound DNA. It was found that [d(TGGGGT)]4 showed a binding preference to the flavonoid glycosides over flavonoid aglycones. It was deduced that glycosylation played a key role for the [d(TGGGGT)]4‐binding properties of flavonoid glycosides. Upon collision‐induced dissociation, complexes of flavonoid/[d(TGGGGT)]4 underwent the loss of flavonoids, suggesting an end‐stacking binding mode. The current work demonstrates that ESI‐MS is a powerful tool in the study of interaction between drugs and nucleic acids.
No preview · Article · Jul 2012 · Chinese Journal of Chemistry
[Show abstract][Hide abstract] ABSTRACT: In this study, electrospray ionization mass spectrometry (ESI-MS) was used to investigate the binding interaction of six alkaloids with parallel intermolecular G-quadruplex [d(TGGGGT)](4), and five alkaloids including berberine, jatrorrhizine, palmatine, tetrandrine, and fangchinoline showed complexation with the target DNA. Relative binding affinities were estimated on the basis of mass spectrometric data. The slight differences in chemical structures of berberine, jatrorrhizine, and palmatine had little influence on their binding affinities to [d(TGGGGT)](4). Tetrandrine and fangchinoline selectively bound to [d(TGGGGT)](4) versus duplex DNA. Collision-induced dissociation (CID) experiments showed that the complexes with berberine, jatrorrhizine, and palmatine dissociated via strand separation and ligand retaining in the strand while the complexes with tetrandrine and fangchinoline were dissociated via ligand elimination. A comparison of dissociation patterns in CID experiments of complexes with the alkaloids to those with the traditional G-quadruplex DNA binders suggested an end-stacking binding mode for tetrandrine and fangchinoline and an intercalation binding mode for berberine, jatrorrhizine, and palmatine to the target DNA. The current work not only provides deep insight into alkaloid/[d(TGGGGT)](4) complexes and useful guidelines for design of efficient anticancer agents but also demonstrates the utility of ESI-MS as a powerful tool for evaluating interaction between ligand and quadruplex DNA.
No preview · Article · Jun 2012 · Journal of Mass Spectrometry
[Show abstract][Hide abstract] ABSTRACT: A novel ligand fishing assay was established to screen triplex DNA binders from complicated samples by a combination of immobilization of triplex DNA on agarose beads and high-performance liquid chromatography-electrospray ionization-mass spectrometry (HPLC-ESI-MS). The biotinylated oligodeoxynucleotides were first bound to the streptavidin agarose beads and then incubated with the duplex DNA as the baits for ligand fishing. This assay was validated by the testing ligand library consisting of coralyne, ethidium bromide, vitexin, and formononetin. The binding affinities of ligands to target DNA were also obtained based on the calibration curves of ligands. Two components (berberine and palmatine) in the extract of Phellodendron chinense Schneid cortexes were fished out as triplex DNA binders by this assay, which indicated its feasibility for screening triplex DNA binders from complicated samples. This preliminary assay can be used for not only screening binders of triplex DNA from natural products extracts but also can obtain their binding affinity information.
No preview · Article · Mar 2012 · Analytical Chemistry