Shape-selective binding of geometrically-constrained bis-distamycins to a DNA duplex and a model Okazaki fragment of identical sequence

William H. Gmeiner, Wei Cui, Sanjay Sharma, Ana Maria Soto, Luis A Marky, J. William Lown

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The binding of ligands to nucleic acids is of great interest for the control of gene expression and other nucleic acid mediated processes. We have evaluated the binding of several geometrically-constrained bis-distamycins to a model Okazaki fragment [OKA], or a DNA duplex having identical base sequence [DD], using gel-shift assays, optical spectroscopy and differential scanning calorimetry. In the case of covalent attachment of two distamycins to a central benzene ring, a similar binding profile was observed for [DD] as was observed for [OKA] (para binds [K(app) > 10 6 M -1 ], meta binds only weakly). For a central pyridyl ring, however, clear distinction between the binding to [DD] and binding to [OKA] was observed. While none of the three meta isomers having a central pyridyl ring bound [OKA], two of them (MT-17 and MT-12) bound [DD] [K(app) > 10 6 M -1 ]. These results demonstrate subtle differences in lexitropsin shape and placement of electronegative atoms may result in selective binding to a nucleic acid duplex based both on base sequence and chemical composition. Selective binding to DNA duplexes may be useful for designing ligands that regulate transcription, but do not interfere in other nucleic acid mediated processes.

Original languageEnglish (US)
Pages (from-to)1365-1379
Number of pages15
JournalNucleosides, Nucleotides and Nucleic Acids
Volume19
Issue number8
DOIs
StatePublished - Jan 1 2000

Fingerprint

Distamycins
Nucleic Acids
DNA
Application programs
Ligands
Differential Scanning Calorimetry
Transcription
Benzene
Gene expression
Isomers
Differential scanning calorimetry
Assays
Spectrum Analysis
Gels
Gene Expression
Atoms
Okazaki fragments
Chemical analysis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Genetics

Cite this

Shape-selective binding of geometrically-constrained bis-distamycins to a DNA duplex and a model Okazaki fragment of identical sequence. / Gmeiner, William H.; Cui, Wei; Sharma, Sanjay; Soto, Ana Maria; Marky, Luis A; Lown, J. William.

In: Nucleosides, Nucleotides and Nucleic Acids, Vol. 19, No. 8, 01.01.2000, p. 1365-1379.

Research output: Contribution to journalArticle

Gmeiner, William H. ; Cui, Wei ; Sharma, Sanjay ; Soto, Ana Maria ; Marky, Luis A ; Lown, J. William. / Shape-selective binding of geometrically-constrained bis-distamycins to a DNA duplex and a model Okazaki fragment of identical sequence. In: Nucleosides, Nucleotides and Nucleic Acids. 2000 ; Vol. 19, No. 8. pp. 1365-1379.
@article{bc41a553e32141cca60162403a877055,
title = "Shape-selective binding of geometrically-constrained bis-distamycins to a DNA duplex and a model Okazaki fragment of identical sequence",
abstract = "The binding of ligands to nucleic acids is of great interest for the control of gene expression and other nucleic acid mediated processes. We have evaluated the binding of several geometrically-constrained bis-distamycins to a model Okazaki fragment [OKA], or a DNA duplex having identical base sequence [DD], using gel-shift assays, optical spectroscopy and differential scanning calorimetry. In the case of covalent attachment of two distamycins to a central benzene ring, a similar binding profile was observed for [DD] as was observed for [OKA] (para binds [K(app) > 10 6 M -1 ], meta binds only weakly). For a central pyridyl ring, however, clear distinction between the binding to [DD] and binding to [OKA] was observed. While none of the three meta isomers having a central pyridyl ring bound [OKA], two of them (MT-17 and MT-12) bound [DD] [K(app) > 10 6 M -1 ]. These results demonstrate subtle differences in lexitropsin shape and placement of electronegative atoms may result in selective binding to a nucleic acid duplex based both on base sequence and chemical composition. Selective binding to DNA duplexes may be useful for designing ligands that regulate transcription, but do not interfere in other nucleic acid mediated processes.",
author = "Gmeiner, {William H.} and Wei Cui and Sanjay Sharma and Soto, {Ana Maria} and Marky, {Luis A} and Lown, {J. William}",
year = "2000",
month = "1",
day = "1",
doi = "10.1080/15257770008033058",
language = "English (US)",
volume = "19",
pages = "1365--1379",
journal = "Nucleosides, Nucleotides and Nucleic Acids",
issn = "1525-7770",
number = "8",

}

TY - JOUR

T1 - Shape-selective binding of geometrically-constrained bis-distamycins to a DNA duplex and a model Okazaki fragment of identical sequence

AU - Gmeiner, William H.

AU - Cui, Wei

AU - Sharma, Sanjay

AU - Soto, Ana Maria

AU - Marky, Luis A

AU - Lown, J. William

PY - 2000/1/1

Y1 - 2000/1/1

N2 - The binding of ligands to nucleic acids is of great interest for the control of gene expression and other nucleic acid mediated processes. We have evaluated the binding of several geometrically-constrained bis-distamycins to a model Okazaki fragment [OKA], or a DNA duplex having identical base sequence [DD], using gel-shift assays, optical spectroscopy and differential scanning calorimetry. In the case of covalent attachment of two distamycins to a central benzene ring, a similar binding profile was observed for [DD] as was observed for [OKA] (para binds [K(app) > 10 6 M -1 ], meta binds only weakly). For a central pyridyl ring, however, clear distinction between the binding to [DD] and binding to [OKA] was observed. While none of the three meta isomers having a central pyridyl ring bound [OKA], two of them (MT-17 and MT-12) bound [DD] [K(app) > 10 6 M -1 ]. These results demonstrate subtle differences in lexitropsin shape and placement of electronegative atoms may result in selective binding to a nucleic acid duplex based both on base sequence and chemical composition. Selective binding to DNA duplexes may be useful for designing ligands that regulate transcription, but do not interfere in other nucleic acid mediated processes.

AB - The binding of ligands to nucleic acids is of great interest for the control of gene expression and other nucleic acid mediated processes. We have evaluated the binding of several geometrically-constrained bis-distamycins to a model Okazaki fragment [OKA], or a DNA duplex having identical base sequence [DD], using gel-shift assays, optical spectroscopy and differential scanning calorimetry. In the case of covalent attachment of two distamycins to a central benzene ring, a similar binding profile was observed for [DD] as was observed for [OKA] (para binds [K(app) > 10 6 M -1 ], meta binds only weakly). For a central pyridyl ring, however, clear distinction between the binding to [DD] and binding to [OKA] was observed. While none of the three meta isomers having a central pyridyl ring bound [OKA], two of them (MT-17 and MT-12) bound [DD] [K(app) > 10 6 M -1 ]. These results demonstrate subtle differences in lexitropsin shape and placement of electronegative atoms may result in selective binding to a nucleic acid duplex based both on base sequence and chemical composition. Selective binding to DNA duplexes may be useful for designing ligands that regulate transcription, but do not interfere in other nucleic acid mediated processes.

UR - http://www.scopus.com/inward/record.url?scp=0033744664&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033744664&partnerID=8YFLogxK

U2 - 10.1080/15257770008033058

DO - 10.1080/15257770008033058

M3 - Article

VL - 19

SP - 1365

EP - 1379

JO - Nucleosides, Nucleotides and Nucleic Acids

JF - Nucleosides, Nucleotides and Nucleic Acids

SN - 1525-7770

IS - 8

ER -