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Published May 24, 2000 | public
Journal Article

Strand selective cleavage of DNA by diastereomers of hairpin polyamide-seco-CBI conjugates

Abstract

Pyrrole-imidazole polyamides are synthetic ligands that bind predetermined DNA sequences with subnanomolar affinity. We report the synthesis and characterization of an eight-ring hairpin polyamide conjugated at the turn to both enantiomers of 1-(chloromethyl)-5-hydroxy-1,2-dihydro-3H-benz[e]indole (seco-CBI), an alkylating moiety related to CC-1065. Alkylation yields and specificity were determined on a restriction fragment containing six base pair match and mismatch sites. Alkylation was observed at a single adenine flanking the polyamide binding site, and strand selective cleavage could be achieved based on the enantiomer of seco-CBI chosen. At 1 nM concentrations of polyamide-seco-CBI conjugate, near quantitative cleavage was observed after 12 h. These bifunctional molecules could be useful for targeting coding regions of genes and inhibition of transcription.

Additional Information

© 2000 American Chemical Society. Received December 13, 1999; Publication Date (Web): April 27, 2000. We are grateful to the National Institutes of Health (Grant GM-27681) for research support and a National Research Service Award to A.Y.C. We thank G.M. Hathaway for MALDI-TOF mass spectrometry and Ken Conklin for HRMS.

Additional details

Created:
August 19, 2023
Modified:
October 18, 2023