Sequence Selective Binding to the DNA Major Groove: Tris(1,10-phenanthroline) Metal Complexes Binding to Poly(dG-dC) and Poly(dA-dT)

Abstract

Molecular modelling and energy minimisation calculations that incorporate solvent effects have been used to investigate the complexation of delta and lambda-[Ru(1,10-phenanthroline]2+ to DNA. The most stable binding geometry for both enantiomers is one in which a phenanthroline chelate is positioned in the major groove. The chelate is partially inserted between neighbouring base pairs, but is not intercalated. For delta, though not for lambda, a geometry with two chelates in the major groove is only slightly less favourable. Minor groove binding is shown to be no more favourable than external electrostatic binding. The optimised geometries of the DNA/[Ru(1,10-phenanthroline]2+ complexes enable published linear dichroism spectra to be used to determine the percentage of each enantiomer in the two most favourable major groove sites. For delta 57 +/- 15% and for lambda 82 +/- 7% of bound molecules are in the partially inserted site.

Structures, spectra, and DNA-binding properties of mixed ligand copper(II) complexes of iminodiacetic acid: The novel role of diimine co-ligands on DNA conformation and hydrolytic and oxidative double strand DNA cleavage

“…These changes are typical of a complex bound to DNA through intercalation involving insertion of the aromatic chromophore of the diimine ligands in between the base pairs of DNA. As the extent of hypochromism is commonly consistent with the strength of intercalative interaction [48][49][50], the observed trend in hypochromism, 3 > 2 > 1 reflects the trend in DNA-binding affinities of the complexes. From the observed spectral changes the value of the intrinsic equilibrium DNA-binding constant K b was determined by regression analysis using Eq.…”

Direction of Intercalation of a bis-Ru(II) Complex to DNA Probed by a Minor Groove Binding Molecule 4',6-Diamidino-2-phenylindole

“…17 However, possibility of classic intercalation of any phenanthroline ligands has been ruled out by viscosity measurements. 16 Although partial intercalation from the major groove was suggested by molecular modeling and energy minimization work, 18 a recent NMR and circular dichroism study showed that the interaction between the [Ru(phen) 2 …”

Computer-Aided Drug Design: An Innovative Tool for Modeling

“…The propeller-like ruthenium tris-phenanthroline complexes do show differential binding between A-T and G-C sequences [2] and moreover may exhibit a preference for purine 3', 5' pyrimidine sites in DNA [3]. Perhaps the most intriguin starting point for a molecule upon which to build nucleic acid selectivity is the ubiquitous sper-mine.…”

“…At their lowest level the contributions represent the replacement of crude mechanical models by displays of structure which are a much more accurate reflection of molecular reality capable of demonstrating motion and solvent effects [1][2][3]. Beyond this, theoretical calculations permit the computation of binding free energies and other relevant molecular properties.…”

“…This latest advance has permitted explicit solvent effects to be incorporated. Underpinning all this work is the availability of high quality computer graphics, largely supported on workstations [1][2][3][4][5].…”