Highly efficient synthesis of DNA-binding polyamides using a convergent fragment-based approach

Org Lett. 2014 Sep 5;16(17):4654-7. doi: 10.1021/ol502203y. Epub 2014 Aug 27.

Abstract

Two advances in the synthesis of hairpin pyrrole-imidazole polyamides (PAs) are described. First, the application of a convergent synthetic strategy is shown, involving the Boc-based solid phase synthesis of a C-terminal fragment and the solution phase synthesis of the N-terminal fragment. Second a new hybrid resin is developed that allows for the preparation of hairpin PAs lacking a C-terminal β-alanine tail. Both methods are compatible with a range of coupling reagents and provide a facile, modular route to prepare PA libraries in high yield and crude purity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA / chemistry*
  • Hydrazines / chemistry
  • Imidazoles / chemical synthesis*
  • Imidazoles / chemistry
  • Indicators and Reagents
  • Molecular Structure
  • Nylons / chemical synthesis*
  • Nylons / chemistry
  • Pyrroles / chemical synthesis*
  • Pyrroles / chemistry
  • Solid-Phase Synthesis Techniques

Substances

  • Hydrazines
  • Imidazoles
  • Indicators and Reagents
  • Nylons
  • Pyrroles
  • hydrazine
  • DNA