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  • Title: Regulation of gene expression with pyrrole-imidazole polyamides.
    Author: Melander C, Burnett R, Gottesfeld JM.
    Journal: J Biotechnol; 2004 Aug 26; 112(1-2):195-220. PubMed ID: 15288953.
    Abstract:
    The pyrrole-imidazole (Py-Im) polyamides represent the only available class of small molecules that can be designed to recognize virtually any predetermined DNA sequence. These molecules have affinities and specificities that equal or exceed natural eukaryotic transcriptional regulatory proteins. Studies with model gene systems, and a variety of eukaryotic and viral transcription factors, have shown that these molecules are potent inhibitors of protein-DNA interactions. Polyamides have been shown to regulate gene expression in simple in vitro systems using defined DNA templates and nuclear extracts as a source of the transcriptional machinery. Activation of gene expression has also been achieved in vitro with polyamide-activator peptide conjugates. Most importantly, polyamides are cell permeable and localize in the nucleus in various cultured cell lines and are capable of down regulating target genes in these cells. Polyamides have been shown to bind to their target sites in chromosomal DNA and both gain- and loss-of-function have been observed by targeting repeated DNA sequences in developing Drosophila embryos.
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