Molecular mechanisms and kinetics between DNA and DNA binding ligands

Andy Sischka, Katja Toensing, Rainer Eckel, Sven David Wilking, Norbert Sewald, Robert Ros, Dario Anselmetti

Research output: Contribution to journalArticle

124 Citations (Scopus)

Abstract

Mechanical properties of single double-stranded DNA (dsDNA) in the presence of different binding ligands were analyzed in optical-tweezers experiments with subpiconewton force resolution. The binding of ligands to DNA changes the overall mechanic response of the dsDNA molecule. This fundamental property can be used for discrimination and identification of different binding modes and, furthermore, may be relevant for various processes like nucleosome packing or applications like cancer therapy. We compared the effects of the minor groove binder distamycin-A, a major groove binding α-helical peptide, the intercalators ethidium bromide, YO-1, and daunomycin as well as the bisintercalator YOYO-1 on λ-DIMA. Binding of molecules to the minor and major groove of dsDNA induces distinct changes in the molecular elasticity compared to the free dsDNA detectable as a shift of the overstretching transition to higher forces. Intercalating molecules affect the molecular mechanics by a complete disappearance of the B-S transition and an associated increase in molecular contour length. Significant force hysteresis effects occurring during stretching/relaxation cycles with velocities >10 nm/s for YOYO-1 and >1000 nm/s for daunomycin. These indicate structural changes in the timescale of minutes for the YOYO-DNA and of seconds for the daunomycin-DNA complexes, respectively.

Original languageEnglish (US)
Pages (from-to)404-411
Number of pages8
JournalBiophysical Journal
Volume88
Issue number1
DOIs
StatePublished - Jan 2005
Externally publishedYes

Fingerprint

Daunorubicin
Ligands
DNA
Optical Tweezers
Intercalating Agents
Ethidium
Nucleosomes
Elasticity
Mechanics
Peptides
1,1'-((4,4,7,7-tetramethyl)-4,7-diazaundecamethylene)bis-4-(3-methyl-2,3-dihydro(benzo-1,3-oxazole)-2-methylidene)quinolinium
Neoplasms
Therapeutics

ASJC Scopus subject areas

  • Biophysics

Cite this

Sischka, A., Toensing, K., Eckel, R., Wilking, S. D., Sewald, N., Ros, R., & Anselmetti, D. (2005). Molecular mechanisms and kinetics between DNA and DNA binding ligands. Biophysical Journal, 88(1), 404-411. https://doi.org/10.1529/biophysj.103.036293

Molecular mechanisms and kinetics between DNA and DNA binding ligands. / Sischka, Andy; Toensing, Katja; Eckel, Rainer; Wilking, Sven David; Sewald, Norbert; Ros, Robert; Anselmetti, Dario.

In: Biophysical Journal, Vol. 88, No. 1, 01.2005, p. 404-411.

Research output: Contribution to journalArticle

Sischka, A, Toensing, K, Eckel, R, Wilking, SD, Sewald, N, Ros, R & Anselmetti, D 2005, 'Molecular mechanisms and kinetics between DNA and DNA binding ligands', Biophysical Journal, vol. 88, no. 1, pp. 404-411. https://doi.org/10.1529/biophysj.103.036293
Sischka, Andy ; Toensing, Katja ; Eckel, Rainer ; Wilking, Sven David ; Sewald, Norbert ; Ros, Robert ; Anselmetti, Dario. / Molecular mechanisms and kinetics between DNA and DNA binding ligands. In: Biophysical Journal. 2005 ; Vol. 88, No. 1. pp. 404-411.
@article{cfda9fe000044e2ca1e3a5cdbcb50e78,
title = "Molecular mechanisms and kinetics between DNA and DNA binding ligands",
abstract = "Mechanical properties of single double-stranded DNA (dsDNA) in the presence of different binding ligands were analyzed in optical-tweezers experiments with subpiconewton force resolution. The binding of ligands to DNA changes the overall mechanic response of the dsDNA molecule. This fundamental property can be used for discrimination and identification of different binding modes and, furthermore, may be relevant for various processes like nucleosome packing or applications like cancer therapy. We compared the effects of the minor groove binder distamycin-A, a major groove binding α-helical peptide, the intercalators ethidium bromide, YO-1, and daunomycin as well as the bisintercalator YOYO-1 on λ-DIMA. Binding of molecules to the minor and major groove of dsDNA induces distinct changes in the molecular elasticity compared to the free dsDNA detectable as a shift of the overstretching transition to higher forces. Intercalating molecules affect the molecular mechanics by a complete disappearance of the B-S transition and an associated increase in molecular contour length. Significant force hysteresis effects occurring during stretching/relaxation cycles with velocities >10 nm/s for YOYO-1 and >1000 nm/s for daunomycin. These indicate structural changes in the timescale of minutes for the YOYO-DNA and of seconds for the daunomycin-DNA complexes, respectively.",
author = "Andy Sischka and Katja Toensing and Rainer Eckel and Wilking, {Sven David} and Norbert Sewald and Robert Ros and Dario Anselmetti",
year = "2005",
month = "1",
doi = "10.1529/biophysj.103.036293",
language = "English (US)",
volume = "88",
pages = "404--411",
journal = "Biophysical Journal",
issn = "0006-3495",
publisher = "Biophysical Society",
number = "1",

}

TY - JOUR

T1 - Molecular mechanisms and kinetics between DNA and DNA binding ligands

AU - Sischka, Andy

AU - Toensing, Katja

AU - Eckel, Rainer

AU - Wilking, Sven David

AU - Sewald, Norbert

AU - Ros, Robert

AU - Anselmetti, Dario

PY - 2005/1

Y1 - 2005/1

N2 - Mechanical properties of single double-stranded DNA (dsDNA) in the presence of different binding ligands were analyzed in optical-tweezers experiments with subpiconewton force resolution. The binding of ligands to DNA changes the overall mechanic response of the dsDNA molecule. This fundamental property can be used for discrimination and identification of different binding modes and, furthermore, may be relevant for various processes like nucleosome packing or applications like cancer therapy. We compared the effects of the minor groove binder distamycin-A, a major groove binding α-helical peptide, the intercalators ethidium bromide, YO-1, and daunomycin as well as the bisintercalator YOYO-1 on λ-DIMA. Binding of molecules to the minor and major groove of dsDNA induces distinct changes in the molecular elasticity compared to the free dsDNA detectable as a shift of the overstretching transition to higher forces. Intercalating molecules affect the molecular mechanics by a complete disappearance of the B-S transition and an associated increase in molecular contour length. Significant force hysteresis effects occurring during stretching/relaxation cycles with velocities >10 nm/s for YOYO-1 and >1000 nm/s for daunomycin. These indicate structural changes in the timescale of minutes for the YOYO-DNA and of seconds for the daunomycin-DNA complexes, respectively.

AB - Mechanical properties of single double-stranded DNA (dsDNA) in the presence of different binding ligands were analyzed in optical-tweezers experiments with subpiconewton force resolution. The binding of ligands to DNA changes the overall mechanic response of the dsDNA molecule. This fundamental property can be used for discrimination and identification of different binding modes and, furthermore, may be relevant for various processes like nucleosome packing or applications like cancer therapy. We compared the effects of the minor groove binder distamycin-A, a major groove binding α-helical peptide, the intercalators ethidium bromide, YO-1, and daunomycin as well as the bisintercalator YOYO-1 on λ-DIMA. Binding of molecules to the minor and major groove of dsDNA induces distinct changes in the molecular elasticity compared to the free dsDNA detectable as a shift of the overstretching transition to higher forces. Intercalating molecules affect the molecular mechanics by a complete disappearance of the B-S transition and an associated increase in molecular contour length. Significant force hysteresis effects occurring during stretching/relaxation cycles with velocities >10 nm/s for YOYO-1 and >1000 nm/s for daunomycin. These indicate structural changes in the timescale of minutes for the YOYO-DNA and of seconds for the daunomycin-DNA complexes, respectively.

UR - http://www.scopus.com/inward/record.url?scp=11244337257&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=11244337257&partnerID=8YFLogxK

U2 - 10.1529/biophysj.103.036293

DO - 10.1529/biophysj.103.036293

M3 - Article

C2 - 15516529

AN - SCOPUS:11244337257

VL - 88

SP - 404

EP - 411

JO - Biophysical Journal

JF - Biophysical Journal

SN - 0006-3495

IS - 1

ER -