Superior duplex DNA strand invasion by acridine conjugated peptide nucleic acids

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 -