Characterization of interaction between Bcl-2 oncogene promoter I-Motif DNA and flavonoids using electrospray ionization mass spectrometry and pressure-assisted capillary electrophoresis frontal analysis.

Characterization of interaction between Bcl-2 oncogene promoter I-Motif DNA and flavonoids using electrospray ionization mass spectrometry and pressure-assisted capillary electrophoresis frontal analysis. Talanta. 2020 Aug 01;215:120885 Authors: Yang Y, Fu H, Qian C, Li H, Chen DDY Abstract B-cell lymphoma 2 (Bcl-2) is an antiapoptotic protein which is believed to be a triggering factor in developing human tumors. The Bcl-2 C-rich promoter element has been shown to form the i-motif (IM) via cytosine-cytosine (C-C+) base pair building blocks, which can be targeted through the binding of ligands associated with Bcl-2 expression modulation. In this work, we monitored IM development and thermodynamic stability within the Bcl-2 promoter via circular dichroism (CD) spectroscopy and electrospray ionization mass spectrometry (ESI-MS). The results demonstrated that at an acidic pH, as well as in a crowded molecular environment, the Bcl-2 promoter element predominantly exists in a stable intramolecular IM folded state. We further explored the potential of targeting of the Bcl-2 IM to increase chemotherapeutic efficacy. We first used a rapid ESI-MS screening assay to identify possible ligands, finding that three natural flavonoids (P1, P5 and P6) exhibited a clear affinity for IM binding at 1:1 stoichiometry. Relative to P6, P1 and P5 were expected to form the more stable complexes with the Bcl-2 IM in gas phase according to MS/MS data. We furt...
Source: Talanta - Category: Chemistry Authors: Tags: Talanta Source Type: research