| 研究実績の概要 |
G-quadruplex has been a promising anticancer therapy target, due to its biological roles involved into regulating genome activation and telomere length. Numerous small molecules were reported with G-quadruplex binding affinity, and considered as new chemo-anticancer agent candidates.
In this research, (1) As the increasing potentiality of peptide for G-quadruplex recognition, the conjugation of G4 ligand with peptide to construct new G4 ligand shows promising G4 specificity. Peptide as the linker part was adopted to construct novel ligand cluster. Cyclic naphthalene diimide was adopted as the base G4 ligand, which showed preference for G-quadruplex recognition. Through evaluating the binding affinities (ITC) and melting stability (CD-based Tm measurement); peptide-cNDI dimers were confirme with enhanced preference for recognizing and stabilizing mono G-quadruplex than cNDI monomer; (2) To evaluate the roles of G4 ligand in targeting G-quadruplex structure in cell level, RNA-seq analysis was performed with treating cyclic anthraquinone to cancer cell line SAS, and non-cyclic anthraquinone was adopted as control. Comparing to non-cyclic anthraquinone, cyclic anthraquinone was observed that highly correlated with G-quadruplex related gene network, besides, cyclic anthraquinone also was observed that trigger more up and down regulation of G-quadruplex related genes in mitochondria.
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