Recognition of Chelerythrine to Human Telomeric DNA and RNA G-quadruplexes

• Published in: Scientific reports Vol. 4; no. 1; p. 6767
• Main Authors: Bai, Li-Ping, Hagihara, Masaki, Nakatani, Kazuhiko, Jiang, Zhi-Hong
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 24.10.2014; Nature Publishing Group
• Subjects: 140/58; 639/638/92/147; 639/638/92/610; Benzophenanthridines - chemistry; Benzophenanthridines - metabolism; Chelerythrine; Deoxyribonucleic acid; DNA; DNA - chemistry; DNA - metabolism; DNA Replication; DNA-directed DNA polymerase; G-Quadruplexes; Humanities and Social Sciences; Humans; Melting; Molecular Structure; multidisciplinary; Nucleic Acid Conformation; Oligodeoxyribonucleotides; Potassium; Potassium - chemistry; Ribonucleic acid; RNA; RNA - chemistry; RNA - metabolism; Science; Spectrometry, Mass, Electrospray Ionization; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Spectrophotometry; Telomere - chemistry; Telomere - genetics; Telomere - metabolism
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep06767

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.