title: Intercalative binding of ditercalinium to d(CpGpCpG)2: a theoretical study.
abstract: The structure of the complex formed between ditercalinium, 2,2'-[4,4'-bipiperidine-1,1'-bis-(ethane-1,2-diyl)]bis(10-me thoxy-7H- pyrido[4,3-c]carbazolium) tetramethane sulfonate (NSC 366241), and the self-complementary tetranucleotide duplex d(CpGpCpG)2 has been investigated by means of a novel theoretical approach for modelling the conformational flexibility of nucleic acids. The methodology used is the JUMNA procedure, a molecular mechanics systematics capable of evaluating the internal energy and the interaction energy of a complex formed from a large number of fragments. In the best energy-minimized structures, the piperidinium chains of ditercalinium are located in the major groove of the right-handed oligonucleotide. Calculations show a distortion of the base-paired d(CpGpCpG)2 minihelix consisting of lateral dislocation of one base pair with respect to another along an axis parallel to the long axis; strong propeller twist and tilt of the end base pairs; a collective motion of all base pairs with respect to the helical axis towards the drug; and an overwinding at the exclusion site. The proposed structure of the complex is in good agreement with reported proton NMR data, supporting the feasibility of such model.
authors.affiliation: Laboratoire de Biochimie Théorique (UA 77 CNRS), Institut de Biologie Physico-Chimique, Paris, France.
authors.forename: R
authors.initials: R
authors.lastname: Maroun
authors.forename: M
authors.initials: M
authors.lastname: Delepierre
authors.forename: B P
authors.initials: BP
authors.lastname: Roques
mesh_terms: D002227:Carbazoles / Q000378:metabolism*; D007364:Intercalating Agents; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D009711:Nucleotides / Q000378:metabolism*; D013816:Thermodynamics
chemical_list: D002227:Carbazoles; D007364:Intercalating Agents; D009711:Nucleotides; C042804:ditercalinium