A core facility will be established for the chemical synthesis of short double-helical DNA molecules of variable sequence. Some of these DNA duplexes will contain either 5-methyl cytosine, a ribonucleotide, or a stable isotope at defined positions in the sequence. These products will be studied by a variety of physical methods including high-resolution NMR, solid-state NMR, saturation-transfer EPR, dynamic laser light scattering, fluorescence polarisation anisotropy decay and ODMR in order to investigate the fundamental structural and dynamic principles underlying the sequence-specific recognition of DNA by proteins. In addition short synthetic DNAs will be used for site-directed mutagenesis studies of genetic regulation and in studies on the synthesis of novel sequence-specific intercalative drugs. We propose to construct, to our own design sepcifications, an extremely sophisticated and highly flexible superconducting spectrometer which will be capable of carrying out all the NMR experiments described in this program.
| Edfeldt, N B Fredrik; Harwood, Eric A; Sigurdsson, Snorri Th et al. (2004) Sequence context effect on the structure of nitrous acid induced DNA interstrand cross-links. Nucleic Acids Res 32:2795-801 |
| Edfeldt, N B Fredrik; Harwood, Eric A; Sigurdsson, Snorri Th et al. (2004) Solution structure of a nitrous acid induced DNA interstrand cross-link. Nucleic Acids Res 32:2785-94 |
| Okonogi, T M; Alley, S C; Reese, A W et al. (2002) Sequence-dependent dynamics of duplex DNA: the applicability of a dinucleotide model. Biophys J 83:3446-59 |
| Okonogi, Tamara M; Alley, Stephen C; Harwood, Eric A et al. (2002) Phosphate backbone neutralization increases duplex DNA flexibility: a model for protein binding. Proc Natl Acad Sci U S A 99:4156-60 |
| Hatcher, M E; LeTrong, I; Stenkamp, R et al. (2001) Local dynamics of the CpG step in a DNA crystal. J Am Chem Soc 123:8874-5 |
| Meints, G A; Karlsson, T; Drobny, G P (2001) Modeling furanose ring dynamics in DNA. J Am Chem Soc 123:10030-8 |
| Meints, G A; Drobny, G P (2001) Dynamic impact of methylation at the M. Hhai target site: a solid-state deuterium NMR study. Biochemistry 40:12436-43 |
| Okonogi, T M; Alley, S C; Reese, A W et al. (2000) Sequence-dependent dynamics in duplex DNA. Biophys J 78:2560-71 |
| Harwood, E A; Hopkins, P B; Sigurdsson, S T (2000) Chemical synthesis of cross-link lesions found in nitrous acid treated DNA: a general method for the preparation of N2-substituted 2'-deoxyguanosines. J Org Chem 65:2959-64 |
| Geahigan, K B; Meints, G A; Hatcher, M E et al. (2000) The dynamic impact of CpG methylation in DNA. Biochemistry 39:4939-46 |
Showing the most recent 10 out of 102 publications
