Dataset Information

Naphthalene diimide bis-guanidinio-carbonyl-pyrrole as a pH-switchable threading DNA intercalator.

ABSTRACT: A novel naphthalene diimde analogue (NDI) equipped at the imide positions with two guanidinio-carbonyl-pyrrole (GCP) pendant arms interacted significantly stronger with ds-DNA at pH 5 than at pH 7, due to reversible protonation of the GCP arms. This was consequence of a pH-switchable threading intercalation into ds-DNAs only at pH 5, while at neutral conditions (pH 7) NDI-GCP₂ switched to the DNA minor groove binding. Intriguingly, NDI-GCP₂ was at both pH values studied bound to the ds-RNA major groove, still showing a higher affinity and thermal denaturation effect at pH 5 due to GCP protonation. At excess over the DNA/RNA conjugate NDI-GCP₂ showed also aggregation along the ds-polynucleotide and AFM and DLS demonstrated that NDI-GCP₂ has pronounced ds-DNA condensation ability.

SUBMITTER: Jana P

PROVIDER: S-EPMC7492691 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Naphthalene diimide bis-guanidinio-carbonyl-pyrrole as a pH-switchable threading DNA intercalator.

Jana Poulami P Šupljika Filip F Schmuck Carsten C Piantanida Ivo I

Beilstein journal of organic chemistry 20200908

A novel naphthalene diimde analogue (NDI) equipped at the imide positions with two guanidinio-carbonyl-pyrrole (GCP) pendant arms interacted significantly stronger with ds-DNA at pH 5 than at pH 7, due to reversible protonation of the GCP arms. This was consequence of a pH-switchable threading intercalation into ds-DNAs only at pH 5, while at neutral conditions (pH 7) NDI-GCP<sub>2</sub> switched to the DNA minor groove binding. Intriguingly, NDI-GCP<sub>2</sub> was at both pH values studied bou ...[more]

PMID: 32983268

Similar Datasets

Project description: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 Ru(II), 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 Ru(II) compounds and DNA. We report a structural NMR study on the binuclear Ru(II) intercalator ?,?-B (?,?-[?-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 ?,?-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: ?,?-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 ?,?-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 Ru(2+) 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 ?,?-B with natural calf thymus DNA. The present minor-groove binding mode is proposed to represent the initial surface interactions of binuclear Ru(II) compounds prior to intercalation into AT-rich DNA.

Dataset Information

Naphthalene diimide bis-guanidinio-carbonyl-pyrrole as a pH-switchable threading DNA intercalator.

Publications

Naphthalene diimide bis-guanidinio-carbonyl-pyrrole as a pH-switchable threading DNA intercalator.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets