The thermodynamics of drug-dna interactions: Ethidium bromide and propidium iodide

Wan Yin Chou, Luis A. Marky, Denise Zaunczkowski, Kenneth J. Breslauer

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

We report the first calorimetrically-derived characterization of the thermodynamics of ethidium bromide (EB) and propidium iodide (PI) binding to a series of nucleic acid host duplexes. Our spectroscopic and calorimetric measurements yield the following results: 1) At low salt (16mM Na+) and 25°C, PI binds more strongly than EB to a given host duplex. The magnitude of this PI preference depends only marginally on base sequence, with AT base pairs showing a greater PI preference than GC base pairs. 2) The enhanced binding of PI relative to EB at low salt and 25°C reflects a more favorable entropic driving force for PI binding. 3) The PI binding preference diminishes at higher salt concentrations (216mM). In other words, the binding preference is electrostatic in origin. 4) The salt dependence of the binding constants (∂lnKb/∂ln[Na+]) reveal that PI binds as a dication while EB binds as a monocation. 5) PI and EB both exhibit impressive enthalpy-entropy compensations when they bind to the deoxy homopolymers poly dA poly dT and poly dA poly dU. We have observed a similar enthalpy-entropy compensation for netropsin binding to the poly dA poly dT homopolymer duplex. We therefore conclude that the compensation phenomenon is an intrinsic property of the host duplex rather than reflecting a property of the binding ligand. 6) When either PI or EB bind to the corresponding ribo homopolymer (poly rA poy rU) we do not observe the enthalpy-entropy compensation that characterizes the binding to the deoxy homopolymer. 7) EB and PI both bind more strongly to poly d(AT) o poly d(AT) than to poly d(AU) o poly d(AU). Specifically, the absence of the thymine methyl group in poly d(AU) poly d(AU) reduces the binding constant of both drugs by a factor of four. This reduction in binding is due to a less favorable entropy change.

Original languageEnglish (US)
Pages (from-to)345-362
Number of pages18
JournalJournal of Biomolecular Structure and Dynamics
Volume5
Issue number2
DOIs
StatePublished - Oct 1987

Fingerprint

Ethidium
Propidium
Drug Interactions
Thermodynamics
Entropy
Salts
Base Pairing
Netropsin
Poly A
Thymine
Static Electricity
Nucleic Acids
Ligands

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

The thermodynamics of drug-dna interactions : Ethidium bromide and propidium iodide. / Chou, Wan Yin; Marky, Luis A.; Zaunczkowski, Denise; Breslauer, Kenneth J.

In: Journal of Biomolecular Structure and Dynamics, Vol. 5, No. 2, 10.1987, p. 345-362.

Research output: Contribution to journalArticle

Chou, Wan Yin ; Marky, Luis A. ; Zaunczkowski, Denise ; Breslauer, Kenneth J. / The thermodynamics of drug-dna interactions : Ethidium bromide and propidium iodide. In: Journal of Biomolecular Structure and Dynamics. 1987 ; Vol. 5, No. 2. pp. 345-362.
@article{eaf794c934ee4c3b836356dec8a65f82,
title = "The thermodynamics of drug-dna interactions: Ethidium bromide and propidium iodide",
abstract = "We report the first calorimetrically-derived characterization of the thermodynamics of ethidium bromide (EB) and propidium iodide (PI) binding to a series of nucleic acid host duplexes. Our spectroscopic and calorimetric measurements yield the following results: 1) At low salt (16mM Na+) and 25°C, PI binds more strongly than EB to a given host duplex. The magnitude of this PI preference depends only marginally on base sequence, with AT base pairs showing a greater PI preference than GC base pairs. 2) The enhanced binding of PI relative to EB at low salt and 25°C reflects a more favorable entropic driving force for PI binding. 3) The PI binding preference diminishes at higher salt concentrations (216mM). In other words, the binding preference is electrostatic in origin. 4) The salt dependence of the binding constants (∂lnKb/∂ln[Na+]) reveal that PI binds as a dication while EB binds as a monocation. 5) PI and EB both exhibit impressive enthalpy-entropy compensations when they bind to the deoxy homopolymers poly dA poly dT and poly dA poly dU. We have observed a similar enthalpy-entropy compensation for netropsin binding to the poly dA poly dT homopolymer duplex. We therefore conclude that the compensation phenomenon is an intrinsic property of the host duplex rather than reflecting a property of the binding ligand. 6) When either PI or EB bind to the corresponding ribo homopolymer (poly rA poy rU) we do not observe the enthalpy-entropy compensation that characterizes the binding to the deoxy homopolymer. 7) EB and PI both bind more strongly to poly d(AT) o poly d(AT) than to poly d(AU) o poly d(AU). Specifically, the absence of the thymine methyl group in poly d(AU) poly d(AU) reduces the binding constant of both drugs by a factor of four. This reduction in binding is due to a less favorable entropy change.",
author = "Chou, {Wan Yin} and Marky, {Luis A.} and Denise Zaunczkowski and Breslauer, {Kenneth J.}",
year = "1987",
month = "10",
doi = "10.1080/07391102.1987.10506399",
language = "English (US)",
volume = "5",
pages = "345--362",
journal = "Journal of Biomolecular Structure and Dynamics",
issn = "0739-1102",
publisher = "Adenine Press",
number = "2",

}

TY - JOUR

T1 - The thermodynamics of drug-dna interactions

T2 - Ethidium bromide and propidium iodide

AU - Chou, Wan Yin

AU - Marky, Luis A.

AU - Zaunczkowski, Denise

AU - Breslauer, Kenneth J.

PY - 1987/10

Y1 - 1987/10

N2 - We report the first calorimetrically-derived characterization of the thermodynamics of ethidium bromide (EB) and propidium iodide (PI) binding to a series of nucleic acid host duplexes. Our spectroscopic and calorimetric measurements yield the following results: 1) At low salt (16mM Na+) and 25°C, PI binds more strongly than EB to a given host duplex. The magnitude of this PI preference depends only marginally on base sequence, with AT base pairs showing a greater PI preference than GC base pairs. 2) The enhanced binding of PI relative to EB at low salt and 25°C reflects a more favorable entropic driving force for PI binding. 3) The PI binding preference diminishes at higher salt concentrations (216mM). In other words, the binding preference is electrostatic in origin. 4) The salt dependence of the binding constants (∂lnKb/∂ln[Na+]) reveal that PI binds as a dication while EB binds as a monocation. 5) PI and EB both exhibit impressive enthalpy-entropy compensations when they bind to the deoxy homopolymers poly dA poly dT and poly dA poly dU. We have observed a similar enthalpy-entropy compensation for netropsin binding to the poly dA poly dT homopolymer duplex. We therefore conclude that the compensation phenomenon is an intrinsic property of the host duplex rather than reflecting a property of the binding ligand. 6) When either PI or EB bind to the corresponding ribo homopolymer (poly rA poy rU) we do not observe the enthalpy-entropy compensation that characterizes the binding to the deoxy homopolymer. 7) EB and PI both bind more strongly to poly d(AT) o poly d(AT) than to poly d(AU) o poly d(AU). Specifically, the absence of the thymine methyl group in poly d(AU) poly d(AU) reduces the binding constant of both drugs by a factor of four. This reduction in binding is due to a less favorable entropy change.

AB - We report the first calorimetrically-derived characterization of the thermodynamics of ethidium bromide (EB) and propidium iodide (PI) binding to a series of nucleic acid host duplexes. Our spectroscopic and calorimetric measurements yield the following results: 1) At low salt (16mM Na+) and 25°C, PI binds more strongly than EB to a given host duplex. The magnitude of this PI preference depends only marginally on base sequence, with AT base pairs showing a greater PI preference than GC base pairs. 2) The enhanced binding of PI relative to EB at low salt and 25°C reflects a more favorable entropic driving force for PI binding. 3) The PI binding preference diminishes at higher salt concentrations (216mM). In other words, the binding preference is electrostatic in origin. 4) The salt dependence of the binding constants (∂lnKb/∂ln[Na+]) reveal that PI binds as a dication while EB binds as a monocation. 5) PI and EB both exhibit impressive enthalpy-entropy compensations when they bind to the deoxy homopolymers poly dA poly dT and poly dA poly dU. We have observed a similar enthalpy-entropy compensation for netropsin binding to the poly dA poly dT homopolymer duplex. We therefore conclude that the compensation phenomenon is an intrinsic property of the host duplex rather than reflecting a property of the binding ligand. 6) When either PI or EB bind to the corresponding ribo homopolymer (poly rA poy rU) we do not observe the enthalpy-entropy compensation that characterizes the binding to the deoxy homopolymer. 7) EB and PI both bind more strongly to poly d(AT) o poly d(AT) than to poly d(AU) o poly d(AU). Specifically, the absence of the thymine methyl group in poly d(AU) poly d(AU) reduces the binding constant of both drugs by a factor of four. This reduction in binding is due to a less favorable entropy change.

UR - http://www.scopus.com/inward/record.url?scp=0023423065&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023423065&partnerID=8YFLogxK

U2 - 10.1080/07391102.1987.10506399

DO - 10.1080/07391102.1987.10506399

M3 - Article

C2 - 3271479

AN - SCOPUS:0023423065

VL - 5

SP - 345

EP - 362

JO - Journal of Biomolecular Structure and Dynamics

JF - Journal of Biomolecular Structure and Dynamics

SN - 0739-1102

IS - 2

ER -