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Design synthesis of a sequence-specific DNA cleaving molecule. (Distamycin-EDTA)iron(II)

Schultz, Peter G. and Taylor, John S. and Dervan, Peter B. (1982) Design synthesis of a sequence-specific DNA cleaving molecule. (Distamycin-EDTA)iron(II). Journal of the American Chemical Society, 104 (24). pp. 6861-6863. ISSN 0002-7863. doi:10.1021/ja00388a101.

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The sequence-dependent recognition of nucleic acids by proteins and small molecules is important in the regulation of many biological processes. A large class of these molecules are bifunctional in nature, combining a chemically reactive moiety with a DNA binding unit. One such molecule is the naturally occurring antitumor antibiotic bleomycin, which binds to and cleaves DNA sequence specifically in a reaction that depends on Fe(II) and oxygen. Recently we reported the synthesis of a DNA binding-DNA cleaving molecule, methidiumpropyl-EDTA (MPE). This bifunctional molecule has the DNA intercalator, methidium, tethered to a metal chelator, EDTA. MPE·Fe(II) cleaves double helical DNA in the presence of dithiothreitol (DTT) with efficiencies comparable to those of bleomycin·Fe(Il)/DTT. Unlike bleomycin·Fe(II), MPE·Fe(II) cleaves DNA non-sequence-specifically, consistent with solution studies demonstrating that the intercalator methidium has no overall base composition specificity.

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Dervan, Peter B.0000-0001-8852-7306
Additional Information:© 1982 American Chemical Society. Received August 16, 1982. We are grateful to the National Institutes of Health for grant support (GM-27681). Contribution No. 6678, Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125.
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Division of Chemistry and Chemical Engineering6678
Issue or Number:24
Record Number:CaltechAUTHORS:20160511-153737079
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Official Citation:Design synthesis of a sequence-specific DNA cleaving molecule. (Distamycin-EDTA)iron(II) Peter G. Shultz, John S. Taylor, and Peter B. Dervan Journal of the American Chemical Society 1982 104 (24), 6861-6863 DOI: 10.1021/ja00388a101
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:67029
Deposited By: Victoria Brennan
Deposited On:19 May 2016 21:24
Last Modified:11 Nov 2021 00:26

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