CARB 28 |
| Pyrrole (Py) and imidazole (Im)-containing polyamides are DNA binding ligands which can be designed to bind as antiparallel dimers in the minor groove of DNA at predetermined or cognate sequences. They provide sequence discrimination with equivalent binding affinities to those of nuclear transcription factors and are able to modulate the transcription of selected genes in vitro and in cells. This presentation will describe some of our recent work in developing polyamides as gene control agents. A systematic approach in the design of covalently linked H-pin polyamides, and investigating the chemical nature of the linkage, linker length, and N-terminus functional groups on selectivity and affinity will also be described. The linkages consist of polymethylene groups or ethylene glycol ethers, and the length varies from 6-10 atoms. The N-terminus is composed of a formamido or a pyrrole-2-carboxamido functionality. Six specific compounds were synthesized and their DNA binding properties thoroughly investigated. DNA sequence specificity and binding affinity was analyzed using DNA melting, DNase I footprinting, circular dichroism (CD), isothermal titration calorimetry (ITC), surface plasmon resonance (SPR), and molecular dynamics techniques. Results from these experiments will be presented. |
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Nucleic Acids as Drug Targets
1:40 PM-4:50 PM, Monday, August 20, 2007 BCEC -- 208, Oral
Division of Carbohydrate Chemistry |