期刊
SCIENTIFIC REPORTS
卷 8, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-017-19095-y
关键词
-
资金
- Nanyang Assistant Professor Fellowship [M4080531]
- Singapore Ministry of Education AcRF Tier 2 Research Grant [M4020163]
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)(mu-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 p-stacking of aromatic ligands, and 2) two Pt(II) cores covalently chelated to guanines at both 3'- and 5'-ends.
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