title: Pyrrole-Imidazole Polyamides: Manual Solid-Phase Synthesis.
abstract: 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.
authors.affiliation: Department of Pure and Applied Chemistry, University of Strathclyde, Glasgow, United Kingdom.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Pauff
authors.affiliation: Department of Chemistry, University of Leicester, Leicester, United Kingdom.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Fallows
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom.
authors.forename: Simon P
authors.initials: SP
authors.lastname: Mackay
authors.affiliation: Guangdong Key Laboratory of Nanomedicine, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, People's Republic of China.
authors.forename: Wu
authors.initials: W
authors.lastname: Su
authors.affiliation: Department of Chemistry, University of Leicester, Leicester, United Kingdom.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Cullis
authors.affiliation: Department of Pure and Applied Chemistry, University of Strathclyde, Glasgow, United Kingdom.
authors.forename: Glenn A
authors.initials: GA
authors.lastname: Burley
mesh_terms: D007093:Imidazoles / Q000737:chemistry*; D011073:Polyamines / Q000138:chemical synthesis* / Q000737:chemistry*; D011758:Pyrroles / Q000737:chemistry*
chemical_list: D007093:Imidazoles; D011073:Polyamines; D011758:Pyrroles; C029899:imidazole
keywords: DNA; gene expression; minor groove; pyrrole-imidazole polyamide; solid-phase synthesis