Exploration of the selective recognition of the G-quadruplex in the N-myc oncogene by electrospray ionization mass spectrometry

RATIONALEThe N-myc gene is a member of the MYC family and its amplification is highly correlated with the pathophysiology of cancers. The G-rich sequence, d(AG(3)CG(3)AG(3)AG(3)A), in the first intron of N-myc can form a G-quadruplex structure. Small molecules binding to it with high affinity and selectivity may provide a potential approach to modulate the expression of the N-myc gene. METHODSElectrospray ionization (ESI) mass spectrometry was used to analyze the G-quadruplex formation of the d(AG(3)CG(3)AG(3)AG(3)A) sequence, and to evaluate the binding affinities and selectivities of natural small molecules with the N-myc G-quadruplex. RESULTSEnniatin B was found to have the highest binding affinity with this G-quadruplex within the 12 small molecules. Moreover, it also showed a biased selectivity toward the N-myc G-quadruplex compared with the other five G-quadruplexes derived from C-myc, Bcl2, Chl1, c-kit promoters and telomere G-rich sequences. CONCLUSIONSIn this study, we found a natural small molecule, enniatin B, which could bind to the G-quadruplex of the d(AG(3)CG(3)AG(3)AG(3)A) sequence from the first intron of the N-myc gene with high affinity and selectivity, which may lead to a potential modulation of the N-myc gene. Copyright (c) 2014 John Wiley & Sons, Ltd.