Mechanical Fingerprints of DNA Drug Complexes

Krautbauer, Rupert; Fischerländer, Stefan; Allen, Stephanie; Gaub, Hermann E.

doi:10.1002/1438-5171(200206)3:2/3<97::aid-simo97>3.0.co;2-s

Cited by 46 publications

(58 citation statements)

References 31 publications

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“…27 Recent studies have demonstrated that in the presence of DNA binding drugs, the results of DNA overstretching experiments parallel those obtained in thermal melting experiments, consistent with the force-induced melting model. [28][29][30] Finally, several recent theoretical studies are also consistent with this model. [31][32][33] Models of Polymer Elasticity.…”

Section: Introductionsupporting

confidence: 79%

“…In this binding mode, a molecule is inserted between adjacent stacked bases, increasing the length of the DNA. Single molecule spectroscopy has been used to analyze DNA intercalation 8,30,70,71 as a method of understanding drug binding for cancer therapy. Perhaps the best known intercalative binding drug is ethidium, the solution form of ethidium bromide.…”

Section: Drug Intercalation and Force-induced Meltingmentioning

confidence: 99%

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Mechanisms of DNA binding determined in optical tweezers experiments

McCauley¹,

Williams²

2006

Biopolymers

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The last decade has seen rapid development in single molecule manipulation of RNA and DNA. Measuring the response force for a particular manipulation has allowed the free energies of various nucleic acid structures and configurations to be determined. Optical tweezers represent a class of single molecule experiments that allows the energies and structural dynamics of DNA to be probed up to and beyond the transition from the double helix to its melted single strands. These experiments are capable of high force resolution over a wide dynamic range. Additionally, these investigations may be compared with results obtained when the nucleic acids are in the presence of proteins or other binding ligands. These ligands may bind into the major or minor groove of the double helix, intercalate between bases or associate with an already melted single strand of DNA. By varying solution conditions and the pulling dynamics, energetic and dynamic information may be deduced about the mechanisms of binding to nucleic acids, providing insight into the function of proteins and the utility of drug treatments. © 2006 Wiley Periodicals, Inc. Biopolymers 85:154–168, 2007.This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com

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Section: Introductionsupporting

confidence: 79%

Section: Drug Intercalation and Force-induced Meltingmentioning

confidence: 99%

Mechanisms of DNA binding determined in optical tweezers experiments

McCauley¹,

Williams²

2006

Biopolymers

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“…In contrast, optical tweezers data for this minor groove binder with -DNA (51% GC) indicates an increasing force value of the transition and a slight tilt that indicates a repression of the cooperative effects (Sischka et al, 2004). Similar results were found for netropsin and Hoechst 33258 (Krautbauer et al, 2002a). For the major groove binder, these two effects increase and particularly the B-S-transition is less cooperative.…”

Section: Groove Bindingmentioning

confidence: 99%

Single molecule force spectroscopy on ligand–DNA complexes: from molecular binding mechanisms to biosensor applications

Ros

Eckel

Bartels

et al. 2004

Journal of Biotechnology

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Recent developments in single molecule force spectroscopy (SMFS) allow direct observation and measurements of forces that hold protein-DNA complexes together. Furthermore, the mechanics of double-stranded (ds) DNA molecules in the presence of small binding ligands can be detected. The results elucidate molecular binding mechanisms and open the way for ultra sensitive and powerful biosensor applications.

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“…In Fig. 5, four force-extension curves are presented, exhibiting the different force responses of -DNA to binding of a bis-intercalator ͑YOYO-1͒, 14 an intercalator ͑ethidium bromide͒, 12,15,17 and a minor groove binder acting as an antitumor drug ͑distamycin-A͒. 14 We could unambiguously show that mechanical properties of DNA vary in the presence of different binding agents, which opens new possibilities to use this setup as a singlemolecule biosensor to investigate DNA binding agents and even to identify molecular binding mechanisms.…”

Section: Resultsmentioning

confidence: 99%

“…16 Recently, it has been shown that different binding modes of DNA binders could be identified which allowed deeper insights into the molecular interplay between DNA and small ligands. 15,17 In this article, we introduce a compact and versatile single-beam optical tweezers setup ͑see Fig. 1͒ which is based on a commercial inverted optical microscope.…”

Section: Introductionmentioning

confidence: 99%

Compact microscope-based optical tweezers system for molecular manipulation

Sischka

Eckel

Tœnsing

et al. 2003

Review of Scientific Instruments

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A compact single beam optical tweezers system for force measurements and manipulation of individual double-stranded deoxyribonucleic acid ͑DNA͒ molecules was integrated into a commercial inverted optical microscope. A maximal force of 150 pN combined with a force sensitivity of less than 0.5 pN allows measurements of elastic properties of single molecules which complements and overlaps the force regime accessible with atomic force microscopy ͑AFM͒. The manipulation and measurement performance of this system was tested with individual -DNA molecules and renders new aspects of dynamic forces phenomena with higher precision in contrast to AFM studies. An integrated liquid handling system with a fluid cell allows investigation of the force response of individual DNA molecules in the presence of DNA binding agents. Comparison of YOYO-1-, ethidium bromide intercalated DNA, and distamycin-A complexed DNA revealed accurate and reproducible differences in the force response to an external load. This opens the possibility to use it as a single molecule biosensor to investigate DNA binding agents and even to identify molecular binding mechanisms.

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Mechanical Fingerprints of DNA Drug Complexes

Cited by 46 publications

References 31 publications

Mechanisms of DNA binding determined in optical tweezers experiments

Mechanisms of DNA binding determined in optical tweezers experiments

Single molecule force spectroscopy on ligand–DNA complexes: from molecular binding mechanisms to biosensor applications

Compact microscope-based optical tweezers system for molecular manipulation

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