title: Electrospray ionization mass spectrometry probing of binding affinity of berbamine, a flexible cyclic alkaloid from traditional Chinese medicine, with G-quadruplex DNA.
abstract: BACKGROUND
  Classic G-quadruplex binders typically have a large aromatic core and interact with G-quadruplexes through π-π stacking with the quartets. There are rather few reports on natural flexible cyclic molecule from traditional Chinese medicine which has high binding affinity with G-quadruplex.
  
  
  METHODS
  Electrospray ionization mass spectrometry (ESI-MS) experiments were performed to evaluate the binding affinities of a natural alkaloid, berbamine, with seven G-quadruplexes. Furthermore, we utilized autodock4 analysis to uncover the binding mode of berbamine with the G-quadruplex.
  
  
  RESULTS
  ESI-MS experiments showed that berbamine has the best binding affinity toward the (GGA)8  G-quadruplex compared with the other six G-quadruplexes. Autodock4 analysis indicated that berbamine interacted with the (GGA)8  G-quadruplex through hydrogen bonding and van der Waals forces with a binding site at the lateral groove formed by DG8-DA9-DA15-DG16.
  
  
  CONCLUSIONS
  In this study, we discovered a novel G-quadruplex binder, berbamine, which has high binding affinity toward the (GGA)8  G-quadruplex. This study provided important clues regarding the probing of small molecule from traditional Chinese medicine which can target the G-quadruplex with high affinity.
authors.affiliation: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Department of Chemical Biology, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Tan
authors.forename: Jiang
authors.initials: J
authors.lastname: Zhou
authors.forename: Gu
authors.initials: G
authors.lastname: Yuan
mesh_terms: D044182:Benzylisoquinolines / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D004247:DNA / Q000737:chemistry* / Q000378:metabolism*; D004365:Drugs, Chinese Herbal; D054856:G-Quadruplexes; D008958:Models, Molecular; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D044182:Benzylisoquinolines; D004365:Drugs, Chinese Herbal; D004247:DNA; C027870:berbamine