title: Spectroscopic and biological studies of phenanthroline compounds: selective recognition of gene-promoter G-quadruplex DNAs preferred over duplex DNA.
abstract: G-Quadruplex DNA formed in the promoter regions of proto-oncogenes would block the transcription process and eventually suppress the development of tumors, so compounds that stabilize G-quadruplex DNA are potential antitumor drugs. This article describes the interactions of three phenanthroline compounds, a-c, with proto-oncogene c-kit2 and c-myc G-quadruplex DNAs by means of polymerase chain reaction (PCR) stop assay, fluorescence resonance energy transfer melting (FRET melting) assay, fluorescence indicator displacement (FID) assay, UV/VIS absorption, fluorescence, and circular dichroism (CD) spectroscopies. All three compounds displayed selectivity for the G-quadruplex over duplex, with binding constants (Ka) for the both quadruplexes varying from 0.49×10⁶ to 3.32×10⁶ M⁻¹ (4.1- to 33.2-fold specificity). Compounds a, b, and c were potential stabilizers for the c-kit2 G-quadruplex with the melting-temperature increase (ΔTm) values of 12-15°. CD Spectra indicated that a-c disrupted the structure of c-kit2 G-quadruplex, whereas no significant change was observed for c-myc G-quadruplex.
authors.affiliation: Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Molecular Science, Shanxi University, Taiyuan 030006, PR China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Wang
authors.forename: Chunying
authors.initials: C
authors.lastname: Wei
mesh_terms: D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D031541:Fluorescence Resonance Energy Transfer; D054856:G-Quadruplexes; D010618:Phenanthrolines / Q000737:chemistry* / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D013056:Spectrophotometry, Ultraviolet; D044366:Transition Temperature
chemical_list: D010618:Phenanthrolines; D016271:Proto-Oncogene Proteins c-myc; D004247:DNA; D019009:Proto-Oncogene Proteins c-kit