Molekulární biofyzika a farmakologie
Influence of surface shape on DNA binding of bimetallo helicates
Publikace: JOURNAL OF INORGANIC BIOCHEMISTRY 101, 1937-1945 Autoři: Peberdy, JC., Malina, J., Khalid, S., Hannon, MJ., Rodger, A. Rok: 2007
In order to probe the DNA-helicate interactions responsible for the DNA binding and remarkable changes of the DNA secondary structure induced by a tetracationic bi-metallo helicate [Fe-2(L-1)(3)](4+) (L-1 = C25H20N4), we have designed and synthesised derivatives with hydrophobic methyl groups at different positions on the ligand backbone. Two dimetallo helicates [Fe-2(L-1)(3)](4+) were prepared using ligands L-3 and L-5 with the methyl substituent on, respectively, the 3 and 5 positions of the pyridyl ring thus producing a wider or slightly longer tetracationic DNA binder. UV/visible absorbance, circular and linear dichroism spectroscopies have been used to characterize the interactions of the cylinders with DNA with the aim of investigating any sequence preference or selectivity upon binding. Competitive binding studies using fluorescent dyes Hoechst 33258 (a minor groove binder), ethidium bromide (an intercalator) and a major groove binding cation (cobalt (III) hexammine) which induces the B -> Z transition have been employed to determine the binding geometries of the enantiomers of two methylated helicates (L-3 and L-5) to DNA and compare with the data obtained previously for the unmethylated analogue (L-1). The results demonstrate that the racemic mixtures and the resolved enantiomers of all helicates bind to DNA inducing structural changes. The overall conclusion from the effect of adding these groups to the surface of the parent helicate is that increasing the width (L-3) reduces the DNA binding strength, the bending and coiling effect and the groove selectivity of the enantiomers compared with the parent compound. There is limited evidence to suggest a slight GC sequence preference. Lengthening the helicate (L-5) results in DNA interactions similar to those of the parent compounds, with an increased preference of the P enantiomer for the minor groove indicating an enhancement of mode selectivity. (c) 2007 Elsevier Inc. All rights reserved.