Extended hairpin polyamide motif for sequence-specific recognition in the minor groove of DNA

Abstract

Three-ring polyamides containing N-methylimidazole and N-methylpyrrole amino acids bind sequence-specifically to double-helical DNA by forming side-by-side complexes in the minor groove. Simple pairing rules relate the amino-acid sequence of a pyrrole-imidazole polyamide to its expected DNA target site, and polyamides that target a wide variety of DNA sequences have been synthesized. We have shown previously that two three-ring subunits could be linked together by an aliphatic amino acid, increasing the binding affinity of the polyamide and, in some cases, increasing the length of the target sequence. We set out to determine whether different types of linkers could be used in a single molecule to generate a nine-ring polyamide molecule that would bind to specific DNA sequences.

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