title: Study on noncovalent complexes of alkaloids with DNA duplex using electrospray ionization mass spectrometry.
abstract: BACKGROUND
  DNA is an important molecular target in modern medicine research. Some DNA-binding ligands have been used to treat numerous diseases. Therefore, understanding the interactions of different ligands with DNA and looking for new DNA agents are necessary to develop new drugs.
  
  
  METHODS
  Electrospray ionization mass spectrometry (ESI-MS) in the negative ion mode was used to screen the noncovalent complexes between 11 alkaloids with double helix oligonucleotides at molar ratios 1:1 to 1:4. The relative binding affinities based on the fraction of bound DNA and sequence selectivities of alkaloids towards the duplex were also investigated by ESI-MS. Moreover, tandem mass spectrometry of 5-charged complex ions was used to try to determine DNA-binding modes.
  
  
  RESULTS
  Six alkaloids showed complexation with the selected DNA duplex, i.e., berberine, coptisine, peimine, aconitine, oxysophoridine and cytisine. They showed their binding affinities with d(AACTCCCGGCACAC/GTGTGCCGGGAGTT) in the order of berberine > coptisine > peimine > aconitine, oxysophoridine > cytosine; additional experiments involving collision energy proved this result. Sequence selectivities were not apparent for coptisine, peimine, aconitine and oxysophoridine with four DNA duplexes. The complexes containing berberine and coptisine underwent the predominant loss of the G base. However, for complexes containing the other four alkaloids, they dissociated via the loss of neutral drug. The results confirmed that they may have different binding modes.
  
  
  CONCLUSIONS
  According to experiment data and structural information, the binding mode of individual drugs with DNA was speculated. It was noted that the bindings of alkaloids peimine, aconitine and oxysophoridine with DNA are discovered firstly. This may give a clue to design duplex-binding ligands and be helpful for understanding biological activities of these alkaloids.
authors.affiliation: Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun Center of Mass Spectrometry, Changchun, 130022, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Ma
authors.forename: Fengrui
authors.initials: F
authors.lastname: Song
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Liu
authors.forename: Shuying
authors.initials: S
authors.lastname: Liu
mesh_terms: D000470:Alkaloids / Q000737:chemistry* / Q000378:metabolism*; D003596:Cytosine / Q000737:chemistry / Q000378:metabolism; D004247:DNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics; D008958:Models, Molecular; D011401:Promoter Regions, Genetic / Q000235:genetics; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D000077022:Survivin
chemical_list: D000470:Alkaloids; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin; D003596:Cytosine; D004247:DNA