Identification of binding mechanisms in single molecule-DNA complexes

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

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

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 α-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.

Original languageEnglish (US)
Pages (from-to)1968-1973
Number of pages6
JournalBiophysical Journal
Volume85
Issue number3
StatePublished - Sep 1 2003
Externally publishedYes

Fingerprint

DNA
Ligands
Daunorubicin
Ethidium
Dermatoglyphics
Biosensing Techniques
Spectrum Analysis
Peptides
Single Molecule Imaging
stallimycin
1,1'-((4,4,7,7-tetramethyl)-4,7-diazaundecamethylene)bis-4-(3-methyl-2,3-dihydro(benzo-1,3-oxazole)-2-methylidene)quinolinium
poly(dC-dG)

ASJC Scopus subject areas

  • Biophysics

Cite this

Eckel, R., Ros, R., Ros, A., Wilking, S. D., Sewald, N., & Anselmetti, D. (2003). Identification of binding mechanisms in single molecule-DNA complexes. Biophysical Journal, 85(3), 1968-1973.

Identification of binding mechanisms in single molecule-DNA complexes. / Eckel, Rainer; Ros, Robert; Ros, Alexandra; Wilking, Sven David; Sewald, Norbert; Anselmetti, Dario.

In: Biophysical Journal, Vol. 85, No. 3, 01.09.2003, p. 1968-1973.

Research output: Contribution to journalArticle

Eckel, R, Ros, R, Ros, A, Wilking, SD, Sewald, N & Anselmetti, D 2003, 'Identification of binding mechanisms in single molecule-DNA complexes', Biophysical Journal, vol. 85, no. 3, pp. 1968-1973.
Eckel R, Ros R, Ros A, Wilking SD, Sewald N, Anselmetti D. Identification of binding mechanisms in single molecule-DNA complexes. Biophysical Journal. 2003 Sep 1;85(3):1968-1973.
Eckel, Rainer ; Ros, Robert ; Ros, Alexandra ; Wilking, Sven David ; Sewald, Norbert ; Anselmetti, Dario. / Identification of binding mechanisms in single molecule-DNA complexes. In: Biophysical Journal. 2003 ; Vol. 85, No. 3. pp. 1968-1973.
@article{e1a49bd0f66d4251acd2a119ed67f222,
title = "Identification of binding mechanisms in single molecule-DNA complexes",
abstract = "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 α-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.",
author = "Rainer Eckel and Robert Ros and Alexandra Ros and Wilking, {Sven David} and Norbert Sewald and Dario Anselmetti",
year = "2003",
month = "9",
day = "1",
language = "English (US)",
volume = "85",
pages = "1968--1973",
journal = "Biophysical Journal",
issn = "0006-3495",
publisher = "Biophysical Society",
number = "3",

}

TY - JOUR

T1 - Identification of binding mechanisms in single molecule-DNA complexes

AU - Eckel, Rainer

AU - Ros, Robert

AU - Ros, Alexandra

AU - Wilking, Sven David

AU - Sewald, Norbert

AU - Anselmetti, Dario

PY - 2003/9/1

Y1 - 2003/9/1

N2 - 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 α-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.

AB - 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 α-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.

UR - http://www.scopus.com/inward/record.url?scp=0042823390&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0042823390&partnerID=8YFLogxK

M3 - Article

C2 - 12944309

AN - SCOPUS:0042823390

VL - 85

SP - 1968

EP - 1973

JO - Biophysical Journal

JF - Biophysical Journal

SN - 0006-3495

IS - 3

ER -