Regulation of gene expression by small molecules

Joel M. Gottesfeld, Laura Neely, John W. Trauger, Eldon E. Baird and Peter B. Dervan
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Joel M. Gottesfeld: The Scripps Research Institute
Laura Neely: The Scripps Research Institute
John W. Trauger: California Institute of Technology
Eldon E. Baird: California Institute of Technology
Peter B. Dervan: California Institute of Technology

Nature, 1997, vol. 387, issue 6629, 202-205

Abstract: 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 proteins1. 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-imida-zole polyamides are cell-permeable and can inhibit the transcription of specific genes.

Date: 1997
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DOI: 10.1038/387202a0

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