BIOL 241 |
| Given the potential as therapeutic agents and biological research tools, synthetic transcription factor mimics (STFMs) capable of upregulating specific genes in vivo have attracted considerable interest. Our laboratory has recently reported a cell-permeable STFM - chimera of a hairpin polyamide (HP) acting as a DNA-binding domain (DBD) and a peptoid mimicing an activation domain (AD) - that activates endogenous genes. For a STFM made of a HP-peptoid chimera to efficiently upregulate a specific gene in living cells, the DNA-binding HP needs to bind to promoters of that gene in native chromatin. To identify HPs that are able to bind efficiently and specifically to promoters of chromosomal target genes, we screened HP-Sdex (a dexamethasone derivative) conjugates using reporter gene assays. Hits identified from that primary screen were tested of activity on native genes. Binding specificity to promoters of target genes was examined through genome-wide expression profiling in living cells. |
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Frontiers in Chemical Biology
5:00 PM-7:00 PM, Wednesday, August 22, 2007 BCEC -- Exhibit Hall - B2, Poster
Division of Biological Chemistry |