title: Interactions of Pt-ttpy with G-Quadruplexes Originating from Promoter Region of the c-myc Gene Deciphered by NMR and Gel Electrophoresis Analysis.
abstract: This study provides insights into the interactions of Pt-ttpy, that is, a metallo-organic heterocycle-comprising platinum(II) complex of terpyridine, and G-quadruplexes adopted by G-rich DNA from the transcriptional regulatory element of the c-myc gene, a well-known attractive target for artificial modulation of oncogene expression. A previously noted drug-like potential of Pt-ttpy relies on its antiproliferative activity on cancer cells and its increased selectivity for G-quadruplex binding attributed to the combination of distinct interacting modes. The predominant interaction between the herein used models of a parallel G-quadruplex exhibiting short propeller-type loops and Pt-ttpy occurs through stacking to the outer G-quartets. The presence of adenine versus thymine residue at the 5'-end overhanging region allows the coordinative binding of Pt-ttpy to the G-quadruplex structure. Interestingly, Pt-ttpy triggers the formation of the G-quadruplex even in the absence of cations. Furthermore, NMR-based characterisation revealed common structural features of Pt-ttpy-G-quadruplex complexes in the presence and absence of cations, which indicate that cations may be expelled from the cores of the corresponding structures.
authors.affiliation: Slovenian NMR centre National Institute of Chemistry, Hajdrihova 19, 1000 Ljubljana (Slovenia).
authors.forename: Marko
authors.initials: M
authors.lastname: Trajkovski
authors.forename: Elodie
authors.initials: E
authors.lastname: Morel
authors.forename: Florian
authors.initials: F
authors.lastname: Hamon
authors.forename: Sophie
authors.initials: S
authors.lastname: Bombard
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Teulade-Fichou
authors.forename: Janez
authors.initials: J
authors.lastname: Plavec
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001483:Base Sequence; D004247:DNA / Q000737:chemistry; D004586:Electrophoresis; D054856:G-Quadruplexes / Q000187:drug effects*; D016259:Genes, myc / Q000187:drug effects*; D006801:Humans; D019906:Nuclear Magnetic Resonance, Biomolecular; D009690:Nucleic Acid Conformation / Q000187:drug effects; D009944:Organoplatinum Compounds / Q000737:chemistry / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; C021975:chloroterpyridineplatinum(II); D004247:DNA
keywords: G-quadruplexes; NMR spectroscopy; ligands; platinum; structures