Determining the origin of the stabilization of DNA by 5-aminopropynylation of pyrimidines
Booth, James, Brown, Tom, Vadhia, Sunil J., Lack, Oliver, Cummins, W. Jon, Trent, John O. and Lane, Andrew N. (2005) Determining the origin of the stabilization of DNA by 5-aminopropynylation of pyrimidines. Biochemistry, 44, (12), 4710-4719. (doi: 10.1021/bi047561d)
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Official URL: http://dx.doi.org/10.1021/bi047561d
Description/Abstract
DNA duplexes are stabilized by aminopropynyl modification of pyrimidines at the 5 position. A combination of thermodynamic analyses as a function of ionic strength, NMR, and molecular modeling has been applied to determine the origin of the stabilization. UV melting studies of a dodecamer bearing one, two, or three nonadjacent modified dU and dC and of a single dU(8) in the Dickerson-Drew dodecamer revealed that the modifications are essentially additive in terms of T-m, Delta G, and Delta H, and there is little difference between dU and dC. The free energy change was parsed into electrostatic and nonelectrostatic components, which showed a significant contribution from charge interactions at physiological ionic strength but also a nonelectrostatic contribution that arises in part from hydration. NMR spectroscopy of the modified Dickerson-Drew dodecamer revealed that the conformation of the duplexes is not significantly altered by the modifications, though P-31 NMR shows that the positive charge may affect ionic interactions with the oxygen atoms of the neighboring phosphates. The modified duplex showed significant hydration in both major and minor grooves. The single strands were also analyzed by NMR, which showed evidence of significant stacking interactions in the modified oliconucteotide. Parsing the energy contribution has shown that electrostatics and hydration can produce Substantial increases in thermodynamic stability without significant changes in the conformation of the duplex state. These considerations have significance for the design of oligonucleotides used for hybridization.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | triple-helix formation, p-31 chemical-shift, thermodynamic stability, aqueous-solution, hybrid duplexes, nucleic-acids, rna duplex, 3rdstrand, nmr, dodecamer |
| Related URLs: | http://www.ncbi.nlm.nih.gov/en...med_docsum http://dx.doi.org/10.1021/bi047561d |
| Subjects: | Q Science > QD Chemistry |
| Divisions: | University Structure - Pre August 2011 > School of Chemistry |
| ePrint ID: | 20729 |
| URI: | http://eprints.soton.ac.uk/id/eprint/20729 |
| Deposited On: | 01 Mar 2006 |
| Last Modified: | 01 Jun 2011 14:39 |
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