Mode of drug binding to DNA determined by optical tweezers force spectroscopy

I Tessmer; C G Baumann; G M Skinner; J E Molloy; J G Hoggett; S J B Tendler; S Allen

doi:10.1080/0950034021000057987

Mode of drug binding to DNA determined by optical tweezers force spectroscopy

I Tessmer, C G Baumann, G M Skinner, J E Molloy, J G Hoggett, S J B Tendler, S Allen

Biology

Research output: Contribution to journal › Article › peer-review

Abstract

Optical tweezers were employed to investigate the effects of small DNA-binding molecules on the low-force (less than or equal to15 pN) stretching behaviour of single DNA molecules. As the canonical B-DNA helix is not perturbed in this force regime, the effects on DNA elasticity observed upon drug binding provide useful insight into how DNA-binding drugs may alter in vivo processes. In this study, the effects of agents with different DNA binding modes were analysed. DNA force-extension curves were recorded in the presence of netropsin, a purely minor groove-binding antibiotic drug, ethidium bromide, an intercalating fluorescent dye, and berenil, an antiprotozoal drug proposed to exhibit both intercalative and minor groove-binding modes. Applying an approximation of the worm-like chain model, which describes the low-force stretching behaviour, the results were analysed in terms of the DNA contour length and persistence length. From these single molecule studies it was observed that minor groove-binding and intercalating modes of DNA-binding could be distinguished based on changes to DNA elasticity.

Original language	English
Pages (from-to)	1627-1636
Number of pages	10
Journal	Journal of Modern Optics
Volume	50
Issue number	10
DOIs	https://doi.org/10.1080/0950034021000057987
Publication status	Published - Jul 2003

Keywords

SINGLE-MOLECULE
NETROPSIN
RECOGNITION
ELASTICITY
ETHIDIUM
BERENIL
DISTAMYCIN
AFFINITY
DUPLEX

Access to Document

10.1080/0950034021000057987

Cite this

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title = "Mode of drug binding to DNA determined by optical tweezers force spectroscopy",

abstract = "Optical tweezers were employed to investigate the effects of small DNA-binding molecules on the low-force (less than or equal to15 pN) stretching behaviour of single DNA molecules. As the canonical B-DNA helix is not perturbed in this force regime, the effects on DNA elasticity observed upon drug binding provide useful insight into how DNA-binding drugs may alter in vivo processes. In this study, the effects of agents with different DNA binding modes were analysed. DNA force-extension curves were recorded in the presence of netropsin, a purely minor groove-binding antibiotic drug, ethidium bromide, an intercalating fluorescent dye, and berenil, an antiprotozoal drug proposed to exhibit both intercalative and minor groove-binding modes. Applying an approximation of the worm-like chain model, which describes the low-force stretching behaviour, the results were analysed in terms of the DNA contour length and persistence length. From these single molecule studies it was observed that minor groove-binding and intercalating modes of DNA-binding could be distinguished based on changes to DNA elasticity.",

keywords = "SINGLE-MOLECULE, NETROPSIN, RECOGNITION, ELASTICITY, ETHIDIUM, BERENIL, DISTAMYCIN, AFFINITY, DUPLEX",

author = "I Tessmer and Baumann, {C G} and Skinner, {G M} and Molloy, {J E} and Hoggett, {J G} and Tendler, {S J B} and S Allen",

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T1 - Mode of drug binding to DNA determined by optical tweezers force spectroscopy

AU - Tessmer, I

AU - Baumann, C G

AU - Skinner, G M

AU - Molloy, J E

AU - Hoggett, J G

AU - Tendler, S J B

AU - Allen, S

PY - 2003/7

Y1 - 2003/7

N2 - Optical tweezers were employed to investigate the effects of small DNA-binding molecules on the low-force (less than or equal to15 pN) stretching behaviour of single DNA molecules. As the canonical B-DNA helix is not perturbed in this force regime, the effects on DNA elasticity observed upon drug binding provide useful insight into how DNA-binding drugs may alter in vivo processes. In this study, the effects of agents with different DNA binding modes were analysed. DNA force-extension curves were recorded in the presence of netropsin, a purely minor groove-binding antibiotic drug, ethidium bromide, an intercalating fluorescent dye, and berenil, an antiprotozoal drug proposed to exhibit both intercalative and minor groove-binding modes. Applying an approximation of the worm-like chain model, which describes the low-force stretching behaviour, the results were analysed in terms of the DNA contour length and persistence length. From these single molecule studies it was observed that minor groove-binding and intercalating modes of DNA-binding could be distinguished based on changes to DNA elasticity.

AB - Optical tweezers were employed to investigate the effects of small DNA-binding molecules on the low-force (less than or equal to15 pN) stretching behaviour of single DNA molecules. As the canonical B-DNA helix is not perturbed in this force regime, the effects on DNA elasticity observed upon drug binding provide useful insight into how DNA-binding drugs may alter in vivo processes. In this study, the effects of agents with different DNA binding modes were analysed. DNA force-extension curves were recorded in the presence of netropsin, a purely minor groove-binding antibiotic drug, ethidium bromide, an intercalating fluorescent dye, and berenil, an antiprotozoal drug proposed to exhibit both intercalative and minor groove-binding modes. Applying an approximation of the worm-like chain model, which describes the low-force stretching behaviour, the results were analysed in terms of the DNA contour length and persistence length. From these single molecule studies it was observed that minor groove-binding and intercalating modes of DNA-binding could be distinguished based on changes to DNA elasticity.

KW - SINGLE-MOLECULE

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KW - RECOGNITION

KW - ELASTICITY

KW - ETHIDIUM

KW - BERENIL

KW - DISTAMYCIN

KW - AFFINITY

KW - DUPLEX

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