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  • Title: Regulation of gene expression by small molecules.
    Author: Gottesfeld JM, Neely L, Trauger JW, Baird EE, Dervan PB.
    Journal: Nature; 1997 May 08; 387(6629):202-5. PubMed ID: 9144294.
    Abstract:
    Small molecules that target specific DNA sequences have the potential to control gene expression. Ligands designed for therapeutic application must bind any predetermined DNA sequence with high affinity and permeate living cells. Synthetic polyamides containing N-methylimidazole and N-methylpyrrole amino acids have an affinity and specificity for DNA comparable to naturally occurring DNA-binding proteins. We report here that an eight-ring polyamide targeted to a specific region of the transcription factor TFIIIA binding site interferes with 5S RNA gene expression in Xenopus kidney cells. Our results indicate that pyrrole-imidazole polyamides are cell-permeable and can inhibit the transcription of specific genes.
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