Exploration of a multi-target ligand, dehydroevodiamine, for the recognition of three G-quadruplexes in c-Myb proto-oncogene by ESI-MS

•ESI-MS revealed the formation of three G-quadruplexes from the upstream region of c-Myb transcription start site.•A natural bioactive alkaloid was found to selectively bind with the three c-Myb G-quadruplexes other than long-chain duplex DNA.•HRMS was utilized to investigate the binding competition of dehydroevodiamine in the mixture solution of three G-quadruplexes.

In this research, ESI mass spectrometry was used to probe the formation of G-quadruplexes from three G-rich sequences (S1-S3) in the upstream region of the transcription start site in human c-Myb proto-oncogene. A ligand, dehydroevodiamine, was found for its high binding affinities towards the c-Myb G-quadruplexes. In addition, dehydroevodiamine bound towards the Q1-Q3 with high selectivity over long-chain duplex DNA. High-resolution ESI-MS was utilized to investigate the binding competition of dehydroevodiamine in the mixture solution of Q1-Q3 G-quadruplexes, and it appeared to have the binding affinity in the following order: Q3 ≈ Q1 > Q2, which is consistent with the results in the single G-quadruplex solutions. The properties of dehydroevodiamine gave its potential in the future studies of c-Myb expression regulation.

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