Inhibition of transcription by bisPNA-peptide conjugates

Nucleosides Nucleotides Nucleic Acids. 2003 May-Aug;22(5-8):535-46. doi: 10.1081/ncn-120021953.

Abstract

Homopyrimidine bisPNAs have been reported to arrest transcription elongation by invading double-stranded DNA and forming a stable (PNA)2/DNA complex. We previously reported that attachment of a designed cationic peptide to the bisPNA enhances the efficiency of strand invasion. Here we investigate whether conjugation to cationic peptides can also improve inhibition of transcription. We observe that a conjugate between a bisPNA and a peptide containing eight lysines is a superior agent for inhibition of transcription, but that inhibition of transcription is reduced as pH and the concentration of magnesium are increased. Our studies provide useful characterization of bisPNAs as agents for inhibiting transcription.

Publication types

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

MeSH terms

  • Base Sequence
  • Binding Sites
  • Dimerization
  • Hydrogen-Ion Concentration
  • Kinetics
  • Molecular Weight
  • Osmolar Concentration
  • Peptide Nucleic Acids / chemistry
  • Peptide Nucleic Acids / pharmacology*
  • Peptides / chemistry
  • Peptides / pharmacology*
  • Pyrimidines
  • Transcription, Genetic / drug effects*

Substances

  • Peptide Nucleic Acids
  • Peptides
  • Pyrimidines