Regulation of gene expression by small molecules

Nature. 1997 May 8;387(6629):202-5. doi: 10.1038/387202a0.


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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Binding Sites
  • Cell Line
  • DNA / metabolism*
  • DNA Footprinting
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation / drug effects*
  • Imidazoles / analysis
  • Molecular Structure
  • Nylons / chemistry
  • Nylons / metabolism
  • Nylons / pharmacology*
  • Pyrroles / analysis
  • RNA, Ribosomal, 5S / genetics
  • RNA, Transfer / genetics
  • Transcription Factor TFIIIA
  • Transcription Factors / metabolism
  • Transcription, Genetic / drug effects
  • Xenopus
  • Zinc Fingers


  • DNA-Binding Proteins
  • Imidazoles
  • Nylons
  • Pyrroles
  • RNA, Ribosomal, 5S
  • Transcription Factor TFIIIA
  • Transcription Factors
  • DNA
  • RNA, Transfer
  • N-methylpyrrole
  • 1-methylimidazole