title: Selective recognition of specific G-quadruplex vs. duplex DNA by a phenanthroline derivative.
abstract: A key problem in designing G-quadruplex ligand is how to discriminate quadruplex DNA specifically from other DNAs, searching ligands targeted at special G-quadruplex structure with high selectivity is a major challenge. Herein, a phenanthrolin-dicarboxylate ester (PD) is proved to exhibit selectivity toward parallel and hybrid G-quadruplex structures with propeller and edge-wise loops, over duplex DNA and antiparallel quadruplex structure with diagonal loop. Such preferred binding of PD to these special G-quadruplex structures is possibly resulted from steric hindrance of: (1) the four substituent groups in PD molecule which prevent close interaction with duplex DNA and (2) the diagonal loop above the G-tetrads in antiparallel G-quadruplex which hinder face-to-face stacking of planar phenanthrolin ring to G-tetrads. In line with its stabilizing ability of G-quadruplex, PD molecule exhibit a inhibitory ability telomerase activity, as well as the potent cytotoxic activity against several human cancer cell lines, which makes it an interesting anti-tumor drug lead.
authors.affiliation: National Laboratory for Molecular Sciences, Center for Molecular Sciences, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, Institute of Chemistry Chinese Academy of Sciences, Beijing 100190, PR China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: National Laboratory for Molecular Sciences, Center for Molecular Sciences, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, Institute of Chemistry Chinese Academy of Sciences, Beijing 100190, PR China.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Xiang
authors.affiliation: Center for Chemical Biology, Institute of Chemistry Chinese Academy of Sciences, Beijing 100190, PR China.
authors.forename: Haiyu
authors.initials: H
authors.lastname: Hu
authors.affiliation: National Laboratory for Molecular Sciences, Center for Molecular Sciences, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, Institute of Chemistry Chinese Academy of Sciences, Beijing 100190, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: National Laboratory for Molecular Sciences, Center for Molecular Sciences, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, Institute of Chemistry Chinese Academy of Sciences, Beijing 100190, PR China.
authors.forename: Fengmin
authors.initials: F
authors.lastname: Yang
authors.affiliation: National Laboratory for Molecular Sciences, Center for Molecular Sciences, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, Institute of Chemistry Chinese Academy of Sciences, Beijing 100190, PR China.
authors.forename: Gang
authors.initials: G
authors.lastname: Shen
authors.affiliation: National Laboratory for Molecular Sciences, Center for Molecular Sciences, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, Institute of Chemistry Chinese Academy of Sciences, Beijing 100190, PR China. Electronic address: tangyl@iccas.ac.cn.
authors.forename: Yalin
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Center for Chemical Biology, Institute of Chemistry Chinese Academy of Sciences, Beijing 100190, PR China. Electronic address: cchen@iccas.ac.cn.
authors.forename: Chuanfeng
authors.initials: C
authors.lastname: Chen
mesh_terms: D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry*; D054856:G-Quadruplexes; D006801:Humans; D010618:Phenanthrolines / Q000737:chemistry* / Q000494:pharmacology; D013816:Thermodynamics
chemical_list: D010618:Phenanthrolines; D004247:DNA
keywords: G-quadruplex; Phenanthroline derivative; Selectivity