This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Eckel, R. Articles by Anselmetti, D. Search for Related Content PubMed PubMed Citation Articles by Eckel, R. Articles by Anselmetti, D.

Identification of Binding Mechanisms in Single Molecule–DNA Complexes

Rainer Eckel ^*, Robert Ros ^*, Alexandra Ros ^*, Sven David Wilking , Norbert Sewald  and Dario Anselmetti ^*

^* Experimental Biophysics and Applied Nanosciences, Faculty of Physics, Bielefeld University, 33615 Bielefeld, Germany; and Organic and Bioorganic Chemistry, Faculty of Chemistry, Bielefeld University, 33615 Bielefeld, Germany

Correspondence: Address reprint requests to Robert Ros, Universitätsstrasse 25, 33615 Bielefeld, Germany. Tel: +49-521-1065388; Fax: +49-521-1062959. E-mail: robert.ros{at}physik.uni-bielefeld.de.

Changes in the elastic properties of single deoxyribonucleic acid (DNA) molecules in the presence of different DNA-binding agents are identified using atomic force microscope single molecule force spectroscopy. We investigated the binding of poly(dG-dC) dsDNA with the minor groove binder distamycin A, two supposed major groove binders, an -helical and a 3₁₀-helical peptide, the intercalants daunomycin, ethidium bromide and YO, and the bis-intercalant YOYO. Characteristic mechanical fingerprints in the overstretching behavior of the studied single DNA-ligand complexes were observed allowing the distinction between different binding modes. Docking of ligands to the minor or major groove of DNA has the effect that the intramolecular B-S transition remains visible as a distinct plateau in the force-extension trace. By contrast, intercalation of small molecules into the double helix is characterized by the vanishing of the B-S plateau. These findings lead to the conclusion that atomic force microscope force spectroscopy can be regarded as a single molecule biosensor and is a potent tool for the characterization of binding motives of small ligands to DNA.

This article has been cited by other articles:

				A. Sischka, K. Toensing, R. Eckel, S. D. Wilking, N. Sewald, R. Ros, and D. Anselmetti Molecular Mechanisms and Kinetics between DNA and DNA Binding Ligands Biophys. J., January 1, 2005; 88(1): 404 - 411. [Abstract] [Full Text] [PDF]