Electrospray ionization mass spectrometry probing of binding affinity of berbamine, a flexible cyclic alkaloid from traditional Chinese medicine, with G-quadruplex DNA

摘要

RATIONALE: 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.