Evaluate binding properties of synthetic berbamine derivatives with the PDGFR-β G-quadruplex by ESI-MS

Abstract

Potent G-quadruplex ligands are of great importance to the regulation of G-quadruplex biological functions. Prior to this study, we have found a potential G-quadruplex binder named berbamine from traditional Chinese medicine with moderate binding affinity and stabilization effect on the PDGFR-β G-quadruplex. To further optimize its binding property, ten berbamine derivatives were designed and synthesized in this study. Characterization of the binding properties using ESI-MS demonstrated that eight derivatives displayed remarkably improved binding affinity and stabilization effects on the PDGFR-β G-quadruplex, and bba3Py was the most outstanding one. Our derivatization strategy successfully transformed the less effective G-quadruplex ligand to a much more potent binder for the PDGFR-β G-quadruplex. Thus, the study provided important clues for the optimization of less potent G-quadruplex binders screened from natural products.