title: Enantioselective binding of chiral 1,14-dimethyl[5]helicene-spermine ligands with B- and Z-DNA.
abstract: Duplex DNA adopts a right-handed B-DNA conformation under physiological conditions. Z-DNA, meanwhile, has a left-handed helical structure and is in equilibrium with right-handed B-DNA. We recently reported that the bisnaphthyl maleimide-spermine conjugate (1) induced a B- to Z-DNA transition with high efficiency at low salt concentrations. It was also found that the bisnaphthyl ligand (1) spontaneously transformed into the corresponding [5]helicene derivative (2). Because [5]helicene 2 can potentially be chiral and because the chiral discrimination of B- and Z-DNA is also of interest, we became interested in whether enatiomerically pure [5]helicene-spermine conjugates might discriminate the chirality of B- or Z-DNA. In this study, we have demonstrated an efficient synthesis of chiral DNA-binding ligands by the conjugation of a [5]helicene unit with a spermine unit. These chiral helicene ligands exhibited recognition of B- and Z-DNA, with (P)-3 displaying preference for B-DNA and (M)-3 for Z-DNA. The characteristic features of the helicene-spermine ligands developed in this study include two points: the cationic spermine portion produces electrostatic interactions along the phosphate backbone of the minor groove, and the helicene forms complexes in an end-stacking mode. Such binding modes, together with the thermodynamic parameters, account for the mode of chiral recognition of (P)- and (M)-3 for B- and Z-DNA.
authors: Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors: Genichiro
authors: G
authors: Tsuji
authors: Kyoko
authors: K
authors: Kawakami
authors: Shigeki
authors: S
authors: Sasaki
mesh_terms: D002851:Chromatography, High Pressure Liquid; D059371:DNA, B-Form / Q000737:chemistry*; D043542:DNA, Z-Form / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D008024:Ligands; D008958:Models, Molecular; D013096:Spermine / Q000737:chemistry*; D055672:Static Electricity; D013237:Stereoisomerism; D013816:Thermodynamics
chemical_list: D059371:DNA, B-Form; D043542:DNA, Z-Form; D008024:Ligands; D013096:Spermine
keywords: Chiral recognition; DNA binding ligand; Helicene; Isothermal titration calorimetry; Surface plasmon resonance