title: Studies on the binding of 5-N-methylated quindoline derivative to human telomeric G-quadruplex.
abstract: Quindoline derivatives as telomeric quadruplex ligands have shown good biological activity for telomerase inhibition. In the present study, we used spectroscopic and calorimetric methods to investigate the interactions between a quindoline derivative (5-methyl-11-(2-morpholinoethylamino)-10-H-indolo-[3,2-b]quinolin-5-ium iodide, compound 1) and human telomeric G-quadruplex. The thermodynamic studies using isothermal titration calorimetry (ITC) indicated that their binding process was temperature-dependent and enthalpy-entropy co-driven. The significant negative heat capacity was obtained experimentally from the temperature dependence of enthalpy changes, which was consistent with that from theoretical calculation, and all suggesting significant hydrophobic contribution to the molecular recognition process. Based on the results from UV-vis, ITC, steady-state and time-resolved fluorescence, their binding mode was determined as two ligand molecules stacking on the quartets on both ends of the quadruplex. These results shed light on rational design and development of quindoline derivatives as G-quadruplex binding ligands.
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.forename: Jia-Heng
authors.initials: JH
authors.lastname: Tan
authors.forename: Shuo-Bin
authors.initials: SB
authors.lastname: Chen
authors.forename: Jin-Qiang
authors.initials: JQ
authors.lastname: Hou
authors.forename: Ding
authors.initials: D
authors.lastname: Li
authors.forename: Zhi-Shu
authors.initials: ZS
authors.lastname: Huang
authors.forename: Lian-Quan
authors.initials: LQ
authors.lastname: Gu
mesh_terms: D000470:Alkaloids / Q000737:chemistry*; D002151:Calorimetry; D054856:G-Quadruplexes; D006801:Humans; D007211:Indoles / Q000737:chemistry*; D008024:Ligands; D011804:Quinolines / Q000737:chemistry*; D011806:Quinolinium Compounds / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D016615:Telomere / Q000737:chemistry*
chemical_list: D000470:Alkaloids; D007211:Indoles; D008024:Ligands; D011804:Quinolines; D011806:Quinolinium Compounds; C016712:quindoline