Superior duplex DNA strand invasion by acridine conjugated peptide nucleic acids

Thomas Bentin; Peter E. Nielsen

doi:10.1021/ja029936t

Superior duplex DNA strand invasion by acridine conjugated peptide nucleic acids

Abstract

DNA helix invasion by P-loop forming peptide nucleic acids (PNAs) is extremely sensitive to increased ionic strength as this stabilizes the DNA duplex. To address this, the DNA intercalator 9-aminoacridine was conjugated to helix invading PNAs, and the duplex DNA binding efficiency of such constructs was measured at different ionic strength conditions by electrophoretic mobility shift analysis. Remarkably, at physiogically relevant ionic strength (140 mM K+/10 mM Na+, 2 mM Mg2+), acridine conjugated PNAs showed 20-150-fold superior binding to a cognate sequence target as compared to the conventional PNAs. This enhancement occurred without compromising the sequence specificity of binding. Thus, simply conjugating the DNA intercalator 9-aminoacridine to PNA represents a major step toward the development of helix invading constructs for in vivo applications such as gene targeting.

Original language	English
Journal	Journal of the American Chemical Society
Volume	125
Issue number	21
Pages (from-to)	6378-9
Number of pages	2
ISSN	0002-7863
DOIs	https://doi.org/10.1021/ja029936t
Publication status	Published - 28 May 2003

Keywords

Aminacrine/chemistry
DNA/chemistry
Hydrophobic and Hydrophilic Interactions
Intercalating Agents/chemistry
Osmolar Concentration
Peptide Nucleic Acids/chemistry

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10.1021/ja029936t

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title = "Superior duplex DNA strand invasion by acridine conjugated peptide nucleic acids",

abstract = "DNA helix invasion by P-loop forming peptide nucleic acids (PNAs) is extremely sensitive to increased ionic strength as this stabilizes the DNA duplex. To address this, the DNA intercalator 9-aminoacridine was conjugated to helix invading PNAs, and the duplex DNA binding efficiency of such constructs was measured at different ionic strength conditions by electrophoretic mobility shift analysis. Remarkably, at physiogically relevant ionic strength (140 mM K+/10 mM Na+, 2 mM Mg2+), acridine conjugated PNAs showed 20-150-fold superior binding to a cognate sequence target as compared to the conventional PNAs. This enhancement occurred without compromising the sequence specificity of binding. Thus, simply conjugating the DNA intercalator 9-aminoacridine to PNA represents a major step toward the development of helix invading constructs for in vivo applications such as gene targeting.",

keywords = "Aminacrine/chemistry, DNA/chemistry, Hydrophobic and Hydrophilic Interactions, Intercalating Agents/chemistry, Osmolar Concentration, Peptide Nucleic Acids/chemistry",

author = "Thomas Bentin and Nielsen, {Peter E.}",

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doi = "10.1021/ja029936t",

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volume = "125",

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journal = "Journal of the American Chemical Society",

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TY - JOUR

T1 - Superior duplex DNA strand invasion by acridine conjugated peptide nucleic acids

AU - Bentin, Thomas

AU - Nielsen, Peter E.

PY - 2003/5/28

Y1 - 2003/5/28

N2 - DNA helix invasion by P-loop forming peptide nucleic acids (PNAs) is extremely sensitive to increased ionic strength as this stabilizes the DNA duplex. To address this, the DNA intercalator 9-aminoacridine was conjugated to helix invading PNAs, and the duplex DNA binding efficiency of such constructs was measured at different ionic strength conditions by electrophoretic mobility shift analysis. Remarkably, at physiogically relevant ionic strength (140 mM K+/10 mM Na+, 2 mM Mg2+), acridine conjugated PNAs showed 20-150-fold superior binding to a cognate sequence target as compared to the conventional PNAs. This enhancement occurred without compromising the sequence specificity of binding. Thus, simply conjugating the DNA intercalator 9-aminoacridine to PNA represents a major step toward the development of helix invading constructs for in vivo applications such as gene targeting.

AB - DNA helix invasion by P-loop forming peptide nucleic acids (PNAs) is extremely sensitive to increased ionic strength as this stabilizes the DNA duplex. To address this, the DNA intercalator 9-aminoacridine was conjugated to helix invading PNAs, and the duplex DNA binding efficiency of such constructs was measured at different ionic strength conditions by electrophoretic mobility shift analysis. Remarkably, at physiogically relevant ionic strength (140 mM K+/10 mM Na+, 2 mM Mg2+), acridine conjugated PNAs showed 20-150-fold superior binding to a cognate sequence target as compared to the conventional PNAs. This enhancement occurred without compromising the sequence specificity of binding. Thus, simply conjugating the DNA intercalator 9-aminoacridine to PNA represents a major step toward the development of helix invading constructs for in vivo applications such as gene targeting.

KW - Aminacrine/chemistry

KW - DNA/chemistry

KW - Hydrophobic and Hydrophilic Interactions

KW - Intercalating Agents/chemistry

KW - Osmolar Concentration

KW - Peptide Nucleic Acids/chemistry

U2 - 10.1021/ja029936t

DO - 10.1021/ja029936t

M3 - Journal article

C2 - 12785772

SN - 0002-7863

VL - 125

SP - 6378

EP - 6379

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

IS - 21

ER -

Superior duplex DNA strand invasion by acridine conjugated peptide nucleic acids

Abstract

Keywords

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