Pyrrole-imidazole polyamides: manual solid-phase synthesis

Steven M. Pauff, Andrew J. Fallows, Simon P. Mackay, Wu Su, Paul M. Cullis, Glenn A. Burley

Research output: Chapter in Book/Report/Conference proceedingOther chapter contribution

4 Citations (Scopus)


Pyrrole-imidazole polyamides (PAs) are a family of DNA-binding peptides that bind in the minor groove of double-stranded DNA (dsDNA) in a sequence-selective, programmable fashion. This protocol describes a detailed manual procedure for the solid-phase synthesis of this family of compounds. The protocol entails solution-phase synthesis of the Boc-protected pyrrole (Py) and imidazole (Im) carboxylic acid building blocks. This unit also describes the importance of choosing the appropriate condensing agent to form the amide linkages between each building block. Finally, a monomeric coupling protocol and a fragment-based approach are described that delivers PAs in 13% to 30% yield in 8 days.

Original languageEnglish
Title of host publicationCurrent Protocols in Nucleic Acid Chemistry
Place of PublicationNew York
Number of pages41
Publication statusPublished - 1 Dec 2015


  • DNA
  • gene expression
  • minor groove
  • pyrrole-imidazole polyamide
  • solid-phase synthesis


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