Targeting the minor groove of DNA

Abstract

Small molecules that specifically bind with high affinity to any predetermined DNA sequence in the human genome will be useful tools in molecular biology and, potentially, in human medicine. Pairing rules have been developed to control rationally the sequence specificity of minor groove binding polyamides containing N-methylimidazole and N-methylpyrrole amino acids. Using simple molecular shapes and a two-letter aromatic amino acid code, pyrrole-imidazole polyamides achieve affinities and specificities comparable to DNA-binding proteins.

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