Solution-phase synthesis of pyrrole-imidazole polyamides

David M. Chenoweth, Daniel A. Harki, Peter B. Dervan

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Pyrrole-Imidazole polyamides are DNA-binding molecules that are programmable for a large repertoire of DNA sequences. Typical syntheses of this class of heterocyclic oligomers rely on solid-phase methods. Solid-phase methodologies offer rapid assembly on a micromole scale sufficient for biophysical characterizations and cell culture studies. In order to produce gram-scale quantities necessary for efficacy studies In animals, polyamides must be readily synthesized In solution. An 8-ring hairpin polyamide 1, which targets the DNA sequence 5′-WGWWCW-3′, was chosen for our synthesis studies as this oligomer exhibits androgen receptor antagonism In cell culture models of prostate cancer. A convergent solution-phase synthesis of 1 from a small set of commercially available building blocks Is presented which highlights principles for preparing gram quantities of pyrrole-Imidazole oligomers with minimal chromatography.

Original languageEnglish (US)
Pages (from-to)7175-7181
Number of pages7
JournalJournal of the American Chemical Society
Volume131
Issue number20
DOIs
StatePublished - May 27 2009

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