Threading intercalators bind DNA with high affinities. Here, we describe single-molecule studies on a cell-permeant luminescent dinuclear ruthenium(II) complex that has been previously shown to thread only into short, unstable duplex structures. Using optical tweezers and confocal microscopy, show this threads locks force-extended in two-step mechanism. Detailed kinetic reveal an individual ste...

Platinum-based anticancer drugs act therapeutically by forming DNA adducts, but suffer from severe toxicity and resistance problems, which have not been overcome in spite of decades of research. And yet defined chromatin targets have generally not been considered in the drug development process. Here we designed novel platinum-intercalator species to target a highly deformed DNA site near the n...

Exonuclease III has been shown previously to reveal the binding sites of the antitumor drug cis-diamminedichloroplatinum(II) on DNA. Pretreatment of the same DNA with the intercalator ethidium bromide causes new platinum binding sites to be detected by the exonuclease III method. In particular, a 5'd(G6-D-G2)3' sequence in a 165-base-pair restriction fragment of plasmid pBR322 becomes a preferr...

DNA stretching in the nucleosome core can cause dramatic structural distortions, which may influence compaction and factor recognition in chromatin. We find that the base pair unstacking arising from stretching-induced extreme minor groove kinking near the nucleosome centre creates a hot spot for intercalation and alkylation by a novel anticancer compound. This may have far reaching implication...

We report here the details of G4-FID (G-quadruplex fluorescent intercalator displacement), a simple method aiming at evaluating quadruplex-DNA binding affinity and quadruplex- over duplex-DNA selectivity of putative ligands. This assay is based on the loss of fluorescence upon displacement of thiazole orange from quadruplex- and duplex-DNA matrices. The original protocol was tested using variou...

Cryptolepine, the main alkaloid present in the roots of Cryptolepis sanguinolenta, presents a large spectrum of biological properties. It has been reported to behave like a DNA intercalator with a preference for GC-rich sequences. In this study, dialysis competition assay and mass spectrometry experiments were used to determine the affinity of cryptolepine and neocryptolepine for DNA structures...

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Doxorubicin (Adriamycin) is an autofluorescent anthracycline antibiotic that acts as a DNA intercalator. Following intraneural microinjection of 3 micrograms of doxorubicin into rat tibial nerve, fluorescence microscopy indicated that it is transported retrogradely to anterior horn cell bodies. Subsequently, these motor neurons underwent a progressive subacute degeneration that occurred over a ...