Journal of the American Chemical Society 2011-11-23

Cysteine cyclic pyrrole-imidazole polyamide for sequence-specific recognition in the DNA minor groove.

Hironobu Morinaga, Toshikazu Bando, Toshiki Takagaki, Makoto Yamamoto, Kaori Hashiya, Hiroshi Sugiyama

Index: J. Am. Chem. Soc. 133(46) , 18924-30, (2011)

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Abstract

Pyrrole-imidazole (PI) polyamides are small DNA-binding molecules that can recognize predetermined DNA sequences with high affinity and specificity. Hairpin PI polyamides have been studied intensively; however, cyclic PI polyamides have received less attention, mainly because of difficulties with their synthesis. Here, we describe a novel cyclization method for producing PI polyamides using cysteine and a chloroacetyl residue. The cyclization reaction is complete within 1 h and has a high conversion efficiency. The method can be used to produce long cyclic PI polyamides that can recognize 7 bp DNA sequences. A cyclic PI polyamide containing two β-alanine molecules had higher affinity and specificity than the corresponding hairpin PI polyamide, demonstrating that the cyclic PI polyamides can be used as a new type of DNA-binding molecule.