title: Studies of DNA-binding properties of lafutidine as adjuvant anticancer agent to calf thymus DNA using multi-spectroscopic approaches, NMR relaxation data, molecular docking and dynamical simulation.
abstract: The interactions between lafutidine (LAF) and calf thymus DNA (ctDNA) have been investigated both experimentally and theoretically. UV-vis absorption studies confirmed that LAF binds to ctDNA through non-covalent interactions. Fluorescence quenching and time-resolved fluorescence spectroscopy studies showed that the binding of LAF with ctDNA occurred through static quenching mechanism, resulting in the formation of a LAF-ctDNA complex. The binding constants (K) of the complex were found to be around 103M-1via NMR relaxation rates and fluorescence data, and the calculated thermodynamic parameters indicated that hydrogen bonds and van der Waals forces played major roles in the binding of LAF to ctDNA. The changes in CD spectra indicated that LAF induced a slight perturbation on the base stacking and helicity of B-DNA. A comparative study of the LAF-ctDNA complex with respect to potassium iodide quenching experiments and competition displacement assays with ethidium bromide, acridine orange, and Hoechst 33258 probes suggested that LAF interacted with ctDNA by minor groove mode. Molecular docking analysis further supported the minor groove binding. Molecular dynamics simulation indicated that LAF depart from the C-G region of DNA, but it can steadily bind with the middle part of DNA composed by A-T base pairs.
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu 610065, PR China.
authors.forename: Hongqin
authors.initials: H
authors.lastname: Yang
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu 610065, PR China.
authors.forename: Peixiao
authors.initials: P
authors.lastname: Tang
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu 610065, PR China.
authors.forename: Bin
authors.initials: B
authors.lastname: Tang
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu 610065, PR China.
authors.forename: Yanmei
authors.initials: Y
authors.lastname: Huang
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu 610065, PR China.
authors.forename: Jiawei
authors.initials: J
authors.lastname: He
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu 610065, PR China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Li
authors.affiliation: College of Chemical Engineering, Sichuan University, Chengdu 610065, PR China. Electronic address: lihuilab@sina.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
mesh_terms: D000081:Acetamides / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism*; D002417:Cattle; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D009690:Nucleic Acid Conformation; D010880:Piperidines / Q000737:chemistry / Q000378:metabolism*; D011725:Pyridines / Q000737:chemistry / Q000378:metabolism*; D013816:Thermodynamics
chemical_list: D000081:Acetamides; D000970:Antineoplastic Agents; D010880:Piperidines; D011725:Pyridines; C076948:lafutidine; D004247:DNA; C427203:calf thymus DNA
keywords: Calf thymus DNA; Groove binding; Lafutidine