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Compounds that bind and stabilize selectively human telomeric quadruplex DNA structures are of significant interest due to their potential to inhibit telomerase and to halt tumor cell proliferation. In our previous study, we found that three novel phenanthroline derivatives could induce and stabilize significantly the formation of an antiparallel structure of human telomeric G-quadruplex DNA (G(3)(T(2)AG(3))(3)), moreover, these compounds could bind selectively to G-quadruplex over duplex. In order to understand their binding nature, in this work we investigated the interactions of compounds 1-3 with human telomeric G-quadruplex and i-motif (C(3)(A(2)TC(3))(3)) DNAs together with calf thymus DNAs (ct DNA) by means of absorption, fluorescence and CD spectroscopies and competition dialysis assay. Results showed that all three compounds showed the highest affinity for G-quadruplex structure although with least affinity for ct DNA. Compounds 1-3 could also stabilize the structure of i-motif with an increase in melting temperature (ΔT(m)) of 7.6, 7.2 and 10.1°C, respectively, in the presence of 10 times excess of compounds. Their binding stoichiometric ratios were 2:1 and 1:1 for G-quadruplex and i-motif DNAs, respectively. The thermodynamic parameters results indicated that the binding of compound to either quadruplex or duplex DNAs was entropically driven and hydrophobic force played a major role in the reaction., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The binding mode and mechanism of the interactions between two planar cationic alkaloids chelerythrine (Che) and sanguinarine (San) with calf thymus DNA (ctDNA) were systematically investigated at pH 5.40 using UV-vis absorption spectroscopy, fluorescence spectroscopy and cyclic voltammetry. Che and San show strong fluorescence at 570 and 589 nm, respectively. Che displays fluorescence enhancement with ctDNA whereas the fluorescence of San is quenched on interaction with ctDNA. In addition, UV-vis spectra of both alkaloids show apparent hypochromicity and are bathochromic shifted, indicating that they could intercalate into ctDNA bases. The fluorescence polarization of Che and San increases in the presence of ctDNA, again implying the intercalation of two alkaloids with ctDNA. This conclusion was also supported by the results obtained from anion quenching and cyclic voltammetry. The binding constants of both alkaloids with ctDNA were calculated in the order of 10(5)L/mol. San binds with ctDNA 3-fold stronger than Che. The stoichiometric bindings are five nucleotides per Che or San. Electrostatic binding also exists between the alkaloids and DNA helix. Finally, theoretical calculations show that only certain parts of Che and San molecules intercalate into the DNA helix., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The binding of a Co(III) complex to the decanucleotide d(CCGAATGAGG)(2) containing two pairs of G:A mismatches was studied by 2D-NMR, UV absorption, and molecular modeling. NMR investigations indicate that racemic [Co(phen)(2)(HPIP)]Cl(3) [HPIP=2-(2-hydroxyphenyl) imidazo [4,5-f][1,10] phenanthroline] binds the decanucleotide by intercalation: the HPIP ligand selectively inserts between the stacked bases from the minor groove at the terminal regions and from the major groove at the sheared region. Further, molecular modeling revealed that the recognition shows strong enantioselectivity: the Lambda-isomer preferentially intercalates into the T(6)G(7):A(5)A(4) region from the DNA major groove, while Delta-isomer favors the terminal C(1)C(2):G(10)G(9) region and intercalates from the minor groove. Detailed energy analysis suggests that the steric interaction, especially the electrostatic effect, is the primary determinants of the recognition event. Melting experiments indicate that binding stabilizes the DNA duplex and increases the melting temperature by 9.5 degrees C. The intrinsic binding constant of the complex to the mismatched duplex was determined to be 3.5x105M(-1).

DNA-binding properties of novel binulear copper(II) complex [Cu(2)(Dmbiim)(4)(H(2)O)(2)](ClO(4))(4).6H(2)O, where Dmbiim = 1,1'-Dimethyl-2,2'-biimidazole are investigated using electronic absorption spectroscopy, fluorescence spectroscopy, viscosity measurement and voltammetry. The results show that the copper(II) complex interacts with DNA through minor groove binding. The interaction between the complex and DNA has also been investigated by gel electrophoresis, interestingly, we found that the copper(II) complex can cleave circular plasmid pBR322 DNA efficiently in the presence of AH(2) (ascorbic acid) at pH 8.0 and 37 degrees C.

A study on the minor-groove recognition of B-DNA d(GTCGAC)2 by racemic D,L-[Co(phen)2dpq](3+), where phen and dpq stand for 1,10-phenanthroline and dipyrido [3,2-d:2,3-f]quinoxaline, respectively, was carried out with a one-, two-dimensional (1D, 2D) nuclear magnetic resonance (NMR) methodologies and molecular simulations. NMR investigations revealed that the metal complex intercalates into the DNA base stack from minor groove orientation with dpq as intercalator and dpq ligand participated in the nucleobase stack. Molecular docking simulations of these systems were consistent with the experimental results and revealed that the recognition shows obvious enantioselectivity: the L-isomer is favored at the pyrimidine-purine/purine-pyrimidine region, especially CG/GC sequence, while the D-isomer is favored at the pyrimidine-pyrimidine/purine-purine region, especially TC/AG sequence. Surprisingly, we found that the L-isomer would be enriched when racemic complex was employed. So contrary to general viewpoint, the L-isomer of complex recognized this right hand double helical DNA preferentially. Detailed analysis suggests that it is the electrostatic interactions that determine the steric interactions and then determine the whole recognition event.

Abstract: A study on the minor-groove recognition of B-DNA d(GTCGAC)2 by racemic d,l-[Co(phen)2dpq]3+, where phen and dpq stand for 1,10-phenanthroline and dipyrido [3,2-d:2,3-f]quinoxaline, respectively, was carried out with a one-, two-dimensional (1D, 2D) nuclear magnetic resonance (NMR) methodologies and molecular simulations. NMR investigations revealed that the metal complex intercalates into the DNA base stack from minor groove orientation with dpq as intercalator and dpq ligand participated in the nucleobase stack. Molecular docking simulations of these systems were consistent with the experimental results and revealed that the recognition shows obvious enantioselectivity: the l-isomer is favored at the pyrimidine–purine/purine–pyrimidine region, especially CG/GC sequence, while the d-isomer is favored at the pyrimidine–pyrimidine/purine–purine region, especially TC/AG sequence. Surprisingly, we found that the l-isomer would be enriched when racemic complex was employed. So contrary to general viewpoint, the l-isomer of complex recognized this right hand double helical DNA preferentially. Detailed analysis suggests that it is the electrostatic interactions that determine the steric interactions and then determine the whole recognition event. [Copyright &y& Elsevier]