. The principal theme of this research proposal is the development of modified oligonucleotides that catalyze sequence-specific nucleic acid cleavage under normal cellular conditions. In addition, a study to determine the potential for targeting antisense oligonucleotides against Pneumocystis carinii will be pursued.
Specific aims are: (1) Determine mechanism and establish scope of the iron mediated sequence-specific cleavage of nucleic acids by phenanthroline tethered oligonucleotides; (2) Construct second generation metal binding modified oligonucleotides designed for high specificity redox-mediated interstrand cleavage; (3) Develop combinatorial modified oligonucleotide libraries specifically designed to bind metal ions (Mg2+, Zn2+, or Ca2+) to search for new sequence- specific nucleases; (4) Explore strand-invasion strategies for dsDNA targeting and cleavage; (5) Determine the potential of oligonucleotide appended ligands for metal-mediated DNA interstrand cross- linking; and (6) Investigate P. carinii as a potential target for antisense oligonucleotides.
| Ahmadian, M; Bergstrom, D E (1998) A simple and regioselective synthesis of 13C-methyl-labeled thymidine. Nucleosides Nucleotides 17:1183-90 |
| Ahmadian, M; Zhang, P; Bergstrom, D E (1998) A comparative study of the thermal stability of oligodeoxyribonucleotides containing 5-substituted 2'-deoxyuridines. Nucleic Acids Res 26:3127-35 |
| Luo, J; Bergstrom, D E; Barany, F (1996) Improving the fidelity of Thermus thermophilus DNA ligase. Nucleic Acids Res 24:3071-8 |
