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

Chang, Aileen Y. and Dervan, Peter B. (2000) Strand selective cleavage of DNA by diastereomers of hairpin polyamide-seco-CBI conjugates. Journal of the American Chemical Society, 122 (20). pp. 4856-4864. ISSN 0002-7863. https://resolver.caltech.edu/CaltechAUTHORS:20160510-084943218

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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.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1021/ja994345xDOIArticle
http://pubs.acs.org/doi/abs/10.1021/ja994345xPublisherArticle
ORCID:
AuthorORCID
Dervan, Peter B.0000-0001-8852-7306
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.
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Funding AgencyGrant Number
NIHGM-27681
NIH Predoctoral FellowshipUNSPECIFIED
Issue or Number:20
Record Number:CaltechAUTHORS:20160510-084943218
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20160510-084943218
Official Citation:Strand Selective Cleavage of DNA by Diastereomers of Hairpin Polyamide-seco-CBI Conjugates Aileen Y. Chang and Peter B. Dervan Journal of the American Chemical Society 2000 122 (20), 4856-4864 DOI: 10.1021/ja994345x
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:66839
Collection:CaltechAUTHORS
Deposited By: Victoria Brennan
Deposited On:10 May 2016 19:14
Last Modified:26 Nov 2019 11:15

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