REGULATION OF GENE-EXPRESSION BY SMALL MOLECULES

Small molecules that target specific DNA sequences have the potential to control gene expression. Ligands designed for therapeutic applicati on must bind any predetermined DNA sequence with high affinity and per meate living cells. Synthetic polyamides containing-N-methylimidazole and N-methylpyrrole amino acids have an affinity and specificity for D NA comparable to naturally occurring DNA-binding proteins(1). We repor t here that an eight-ring polyamide targeted to a specific region of t he transcription factor TFIIIA binding site interferes with 5S RNA gen e expression in Xenopus kidney cells. Our results indicate that pyrrol e-imidazole polyamides are cell-permeable and can inhibit the transcri ption of specific genes.