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Regulation of gene expression by small molecules
J M Gottesfeld1, L Neely, J W Trauger
1Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
Nature
|May 8, 1997
Summary
Synthetic polyamides targeting specific DNA sequences can control gene expression. These cell-permeable molecules successfully inhibited 5S RNA gene expression in Xenopus kidney cells.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- Small molecules targeting DNA offer potential for gene expression control.
- Therapeutic ligands require high DNA binding affinity and cell permeability.
- Synthetic polyamides (N-methylimidazole, N-methylpyrrole) show DNA binding comparable to proteins.
Purpose of the Study:
- To investigate the cell permeability and gene expression inhibitory effects of synthetic polyamides.
- To assess the potential of pyrrole-imidazole polyamides as therapeutic agents targeting specific DNA sequences.
Main Methods:
- Design and synthesis of an eight-ring polyamide.
- Targeting the polyamide to the transcription factor TFIIIA binding site.
- Assessing interference with 5S RNA gene expression in Xenopus kidney cells.
Main Results:
- The eight-ring polyamide demonstrated cell permeability in Xenopus kidney cells.
- The polyamide successfully interfered with 5S RNA gene expression.
- Pyrrole-imidazole polyamides were shown to inhibit transcription of specific genes.
Conclusions:
- Pyrrole-imidazole polyamides are cell-permeable and can inhibit specific gene transcription.
- These polyamides hold promise for controlling gene expression through targeted DNA binding.