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Expanding the repertoire of natural product-inspired ring pairs for molecular recognition of DNA.

ABSTRACT: A furan amino acid, inspired by the recently discovered proximicin natural products, was incorporated into the scaffold of a DNA-binding hairpin polyamide. While unpaired oligomers of 2,4-disubstituted furan amino acids show poor DNA-binding activity, furan (Fn) carboxamides paired with N-methylpyrrole (Py) and N-methylimidazole (Im) rings demonstrate excellent stabilization of duplex DNA as well as discrimination of noncognate sequences, consistent with function as a Py mimic according to the Py/Im polyamide pairing rules.

SUBMITTER: Muzikar KA

PROVIDER: S-EPMC3195311 | biostudies-other | 2011 Oct

REPOSITORIES: biostudies-other

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Expanding the repertoire of natural product-inspired ring pairs for molecular recognition of DNA.

Muzikar Katy A KA Meier Jordan L JL Gubler Daniel A DA Raskatov Jevgenij A JA Dervan Peter B PB

Organic letters 20110929 20

A furan amino acid, inspired by the recently discovered proximicin natural products, was incorporated into the scaffold of a DNA-binding hairpin polyamide. While unpaired oligomers of 2,4-disubstituted furan amino acids show poor DNA-binding activity, furan (Fn) carboxamides paired with N-methylpyrrole (Py) and N-methylimidazole (Im) rings demonstrate excellent stabilization of duplex DNA as well as discrimination of noncognate sequences, consistent with function as a Py mimic according to the P ...[more]

PMID: 21957930

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