title: Recognition of chelerythrine to human telomeric DNA and RNA G-quadruplexes.
abstract: A study on binding of antitumor chelerythrine to human telomeric DNA/RNA G-quadruplexes was performed by using DNA polymerase stop assay, UV-melting, ESI-TOF-MS, UV-Vis absorption spectrophotometry and fluorescent triazole orange displacement assay. Chelerythrine selectively binds to and stabilizes the K(+)-form hybrid-type human telomeric DNA G-quadruplex of biological significance, compared with the Na(+)-form antiparallel-type DNA G-quadruplex. ESI-TOF-MS study showed that chelerythrine possesses a binding strength for DNA G-quadruplex comparable to that of TMPyP4 tetrachloride. Both 1:1 and 2:1 stoichiometries were observed for chelerythrine's binding with DNA and RNA G-quadruplexes. The binding strength of chelerythrine with RNA G-quadruplex is stronger than that with DNA G-quadruplex. Fluorescent triazole orange displacement assay revealed that chelerythrine interacts with human telomeric RNA/DNA G-quadruplexes by the mode of end- stacking. The relative binding strength of chelerythrine for human telomeric RNA and DNA G-quadruplexes obtained from ESI-TOF-MS experiments are respectively 6.0- and 2.5-fold tighter than that with human telomeric double-stranded hairpin DNA. The binding selectivity of chelerythrine for the biologically significant K(+)-form human telomeric DNA G-quadruplex over the Na(+)-form analogue, and binding specificity for human telomeric RNA G-quadruplex established it as a promising candidate in the structure-based design and development of G-quadruplex specific ligands.
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, and Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macau.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Bai
authors.affiliation: Regulatory Bioorganic Chemistry, The Institute of Scientific and Industrial Research (SANKEN), Osaka University, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Hagihara
authors.affiliation: Regulatory Bioorganic Chemistry, The Institute of Scientific and Industrial Research (SANKEN), Osaka University, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakatani
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, and Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macau.
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Jiang
mesh_terms: D053119:Benzophenanthridines / Q000737:chemistry* / Q000378:metabolism; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D004261:DNA Replication; D054856:G-Quadruplexes; D006801:Humans; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides; D011188:Potassium / Q000737:chemistry; D012313:RNA / Q000737:chemistry* / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D016615:Telomere / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism
chemical_list: D053119:Benzophenanthridines; D009838:Oligodeoxyribonucleotides; D012313:RNA; D004247:DNA; C016299:chelerythrine; D011188:Potassium