Studies on alkaloids binding to GC-rich human survivin promoter DNA using positive and negative ion electrospray ionization mass spectrometry.
Electrospray ionization mass spectrometry (ESI-MS) was used to investigate the binding of 13 alkaloids to two GC-rich DNA duplexes which are critical sequences in human survivin promoter. Negative ion ESI-MS was first applied to screen the binding of the alkaloids to the duplexes. Six alkaloids (including berberine, jatrorrhizine, palmatine, reserpine, berbamine, and tetrandrine) show complexation with the target DNA sequences. Relative binding affinities were estimated from the negative ion ESI data, and the alkaloids show a binding preference to the duplex with higher GC content. Positive ion ESI mass spectra of the complexes were also recorded and compared with those obtained in negative ion mode. Only the 1 : 1 complex with berbamine was observed with lower abundance in the positive ion mass spectrum while complexes with the other alkaloids were absolutely absent. Collision-induced dissociation (CID) experiments indicate that the complexes with the protoberberine alkaloids (berberine, jatrorrhizine, and palmatine) dissociate via base loss and covalent cleavage. In contrast, product ion spectra of the complexes with the alkaloids reserpine, berbamine, and tetrandrine show the predominant loss of a neutral alkaloid molecule, accompanied by base loss and covalent cleavage to a lesser extent. A comparison of the gas-phase behaviors of complexes with the alkaloids to those with the traditional DNA binders has suggested an intercalative binding mode of these alkaloids to the target DNA duplexes.
Wang
Zhaofu
Z
Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun Center of Mass Spectrometry, Changchun, 130022, P R China.
Guo
Xinhua
X
Liu
Zhiqiang
Z
Cui
Meng
M
Song
Fengrui
F
Liu
Shuying
S
D000470:Alkaloids / Q000737:chemistry* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000737:chemistry; D001482:Base Composition / Q000235:genetics; D044182:Benzylisoquinolines / Q000737:chemistry; D001599:Berberine / Q000031:analogs & derivatives / Q000737:chemistry; D001600:Berberine Alkaloids / Q000737:chemistry; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D020862:GC Rich Sequence / Q000235:genetics; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D007364:Intercalating Agents / Q000737:chemistry; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D015394:Molecular Structure; D009363:Neoplasm Proteins / Q000235:genetics*; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012110:Reserpine / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D000077022:Survivin; D053719:Tandem Mass Spectrometry
D000470:Alkaloids; D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D044182:Benzylisoquinolines; D001600:Berberine Alkaloids; D051034:Inhibitor of Apoptosis Proteins; D007364:Intercalating Agents; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D009838:Oligodeoxyribonucleotides; D000077022:Survivin; C055785:jatrorrhizine; D001599:Berberine; C009438:tetrandrine; D012110:Reserpine; D004247:DNA; C005413:palmatine; C027870:berbamine