Dual functional dinuclear platinum complex with selective reactivity towards c-myc G-quadruplex.

ABSTRACT: G-quadruplexes (GQ) folded by the oncogenic G-rich sequences are the promising targets for developing anticancer therapeutic molecules. However, the current drug development mainly focused on non-covalent dynamic binders to stabilize GQ structures, while the covalent targeting from inorganic complexes via chelating principles, as a potent therapeutic strategy was surprisingly lack of exploration. Herein, a series of dinuclear platinum complexes, [(Pt(Dip)Cl)2(?-diamine)](NO3)2 (Dip: 4,7-diphenyl-1,10-phenanthroline), were designed to contain two dual-functional Pt cores connected by an alkyl linkage. Pt3 with nonanediamine linkage optimized the specific binding towards c-myc G-quadruplex via dual functional clamp on GQ as 1) non-covalently ?-stacking of aromatic ligands, and 2) two Pt(II) cores covalently chelated to guanines at both 3'- and 5'-ends.

SUBMITTER: He L 

PROVIDER: S-EPMC5768759 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature