Hybridization of PNA to Structured DNA Targets: Quadruplex Invasion and the Overhang Effect
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- 作者：Bhaskar Datta and Bruce A. Armitage
- 刊名：Journal of the American Chemical Society
- 出版年：2001
- 出版时间：October 3, 2001
- 年：2001
- 卷：123
- 期：39
- 页码：9612 - 9619
- 全文大小：91K
- 年卷期：v.123,no.39(October 3, 2001)
- ISSN：1520-5126
文摘
Peptide nucleic acid (PNA) probes have been synthesized and targeted to quadruplex DNA. UV-vis and CD spectroscopy reveal that the quadruplex structure of the thrombin binding aptamer (TBA) is disruptedat 37 
C by a short PNA probe. The corresponding DNA probe fails to bind to the stable secondary structureat this temperature. Thermal denaturation experiments indicate surprisingly high thermal and thermodynamicstabilities for the PNA-TBA hybrid. Our results point to the nonbonded nucleobase overhangs on the DNAas being responsible for this stability. This "overhang effect" is found for two different PNA-DNA sequencesand a variety of different overhang lengths and sequences. The stabilization offered by the overhangs assiststhe PNA in overcoming the stable secondary structure of the DNA target, an effect which may be significantin the targeting of biological nucleic acids, which will always be much longer than the PNA probe. The abilityof PNA to invade a structured DNA target expands its potential utility as an antigene agent or hybridizationprobe.
C by a short PNA probe. The corresponding DNA probe fails to bind to the stable secondary structureat this temperature. Thermal denaturation experiments indicate surprisingly high thermal and thermodynamicstabilities for the PNA-TBA hybrid. Our results point to the nonbonded nucleobase overhangs on the DNAas being responsible for this stability. This "overhang effect" is found for two different PNA-DNA sequencesand a variety of different overhang lengths and sequences. The stabilization offered by the overhangs assiststhe PNA in overcoming the stable secondary structure of the DNA target, an effect which may be significantin the targeting of biological nucleic acids, which will always be much longer than the PNA probe. The abilityof PNA to invade a structured DNA target expands its potential utility as an antigene agent or hybridizationprobe.