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Initial DNA Interactions of the Binuclear Threading Intercalator Λ,Λ-[μ-bidppz(bipy)4Ru2]4+: An NMR Study with [d(CGCGAATTCGCG)]2

Lisha Wu (Institutionen för kemi- och bioteknik, Fysikalisk kemi) ; Anna Reymer (Institutionen för kemi- och bioteknik, Fysikalisk kemi) ; Cecilia Persson ; Krzysztof Kazimierczuk ; Tom Brown ; Per Lincoln (Institutionen för kemi- och bioteknik, Fysikalisk kemi) ; Bengt Nordén (Institutionen för kemi- och bioteknik, Fysikalisk kemi) ; Martin Billeter
Chemistry - A European Journal (0947-6539). Vol. 19 (2013), 17, p. 5401-5410.
[Artikel, refereegranskad vetenskaplig]

Binuclear polypyridine ruthenium compounds have been shown to slowly intercalate into DNA, following a fast initial binding on the DNA surface. For these compounds, intercalation requires threading of a bulky substituent, containing one RuII, through the DNA base-pair stack, and the accompanying DNA duplex distortions are much more severe than with intercalation of mononuclear compounds. Structural understanding of the process of intercalation may greatly gain from a characterisation of the initial interactions between binuclear RuII compounds and DNA. We report a structural NMR study on the binuclear RuII intercalator L,L-B (L,L-[m-bidppz- (bipy)4Ru2] 4+; bidppz=11,11’-bis(dipyrido[3,2-a:2’,3’-c]phenazinyl, bipy = 2,2’-bipyridine) mixed with the palindromic DNA [d(CGCGAATTCGCG)]2. Threading of L,L-B depends on the presence and length of AT stretches in the DNA. Therefore, the latter was selected to promote initial binding, but due to the short stretch of AT base pairs, final intercalation is prevented. Structural calculations provide a model for the interaction: L,L-B is trapped in a well-defined surface-bound state consisting of an eccentric minor-groove binding. Most of the interaction enthalpy originates from electrostatic and van der Waals contacts, whereas intermolecular hydrogen bonds may help to define a unique position of L,L-B. Molecular dynamics simulations show that this minor-groove binding mode is stable on a nanosecond scale. To the best of our knowledge, this is the first structural study by NMR spectroscopy on a binuclear Ru compound bound to DNA. In the calculated structure, one of the positively charged Ru2+ moieties is near the central AATT region; this is favourable in view of potential intercalation as observed by optical methods for DNA with longer AT stretches. Circular dichroism (CD) spectroscopy suggests that a similar binding geometry is formed in mixtures of L,L-B with natural calf thymus DNA. The present minor-groove binding mode is proposed to represent the initial surface interactions of binuclear RuII compounds prior to intercalation into ATrich DNA.

Nyckelord: DNA, intercalation, NMR, ruthenium

Denna post skapades 2013-04-15. Senast ändrad 2017-01-30.
CPL Pubid: 175713


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Institutioner (Chalmers)

Institutionen för kemi- och bioteknik, Fysikalisk kemi (2005-2014)
Svenskt NMR-centrum vid Göteborgs universitet (GU)
Institutionen för kemi och molekylärbiologi (GU)


Biofysikalisk kemi
Molekylär biofysik

Chalmers infrastruktur



Denna publikation är ett resultat av följande projekt:

Supramolecular motive power (SUMO) (EC/FP7/227700)