title: A dual-site simultaneous binding mode in the interaction between parallel-stranded G-quadruplex [d(TGGGGT)]4 and cyanine dye 2,2'-diethyl-9-methyl-selenacarbocyanine bromide.
abstract: G-quadruplexes have attracted growing attention as a potential cancer-associated target for both treatment and detection in recent years. For detection purpose, high specificity is one of the most important factors to be considered in G-quadruplex probe design. It is well known that end stacking and groove binding are two dominated quadruplex-ligand binding modes, and currently most reported G-quadruplex probes are designed based on the former, which has been proven to show good selectivity between quadruplexes and non-quadruplexes. Because groove of G-quadruplex also has some unique chemical properties, it could be inferred that probes that can interact with both the groove and G-tetrad site of certain G-quadruplexes simultaneously might possess higher specificity in aspects of discriminating different quadruplexes. In this article, we report a cyanine dye as a potential novel probe scaffold that could occupy both the 5'-end external G-tetrad and the corresponding groove of the G-quadruplex simultaneously. By using various spectrum and nuclear magnetic resonance techniques, we give a detailed binding characterization for this dual-site simultaneous binding mode. A preliminary result suggests that this mode might provide highly specific recognition to a parallel-stranded G-quadruplex. These findings and the structural elucidation might give some clues in aspects of developing highly specific G-quadruplex probes.
authors.affiliation: Beijing National Laboratory for Molecular Sciences (BNLMS), Center for Molecular Sciences, State Key Laboratory for Structural Chemistry for Unstable and Stable Species, Institute of Chemistry, Chinese Academy of Sciences (ICCAS), Beijing 100190, PR China and Department of Chemistry, University of Chinese Academy of Sciences, Beijing 100049, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Gai
authors.forename: Qianfan
authors.initials: Q
authors.lastname: Yang
authors.forename: Junfeng
authors.initials: J
authors.lastname: Xiang
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.forename: Hongxia
authors.initials: H
authors.lastname: Sun
authors.forename: Aijiao
authors.initials: A
authors.lastname: Guan
authors.forename: Qian
authors.initials: Q
authors.lastname: Shang
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Yalin
authors.initials: Y
authors.lastname: Tang
mesh_terms: D001665:Binding Sites; D002232:Carbocyanines / Q000737:chemistry*; D019281:Dimerization; D005456:Fluorescent Dyes / Q000737:chemistry*; D054856:G-Quadruplexes; D056004:Molecular Dynamics Simulation; D019906:Nuclear Magnetic Resonance, Biomolecular
chemical_list: C580882:2,2'-diethyl-9-methylselenacarbocyanine; D002232:Carbocyanines; D005456:Fluorescent Dyes