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Chromomycin, mithramycin, and olivomycin binding sites on heterogeneous DNA. Footprinting with methidiumpropyl-EDTA•iron(II)

Van Dyke, Michael W. and Dervan, Peter B. (1983) Chromomycin, mithramycin, and olivomycin binding sites on heterogeneous DNA. Footprinting with methidiumpropyl-EDTA•iron(II). Biochemistry, 22 (10). pp. 2373-2377. ISSN 0006-2960. doi:10.1021/bi00279a011.

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The DNA binding sites for the antitumor, antiviral, antibiotics chromomycin, mithramycin, and olivomycin on 70 base pairs of heterogeneous DNA have been determined by using the (methidiumpropyl-EDTA)iron(II) [MPE•Fe(II)] DNA cleavage inhibition pattern technique. Two DNA restriction fragments 117 and 168 base pairs in length containing the lactose operon promoter-operator region were prepared with complementary strands labeled with ^(32)P at the 3' end. MPE•Fe(II) was allowed to partially cleave the restriction fragment preequilibrated with either chromomycin, mithramycin, or olivomycin in the presence of Mg^(2+). The preferred binding sites for chromomycin, mithramycin, and olivomycin in the presence of Mg^(2+) appear to be a minimum of 3 base pairs in size containing at least 2 contiguous dG•dC base pairs. Many binding sites are similar for the three antibiotics; chromomycin and olivomycin binding sites are nearly identical. The number of sites protected from MPE•Fe(II) cleavage increases as the concentration of drug is raised. For chromomycin/Mg^(2+), the preferred sites on the 70 base pairs of DNA examined are (in decreasing affinity) 3'-GGG, CGA > CCG, GCC > CGA, CCT > CTG-5'. The sequence 3'-CGA-5' has different affinities, indicating the importance of either flanking sequences or a nearly bound drug.

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Dervan, Peter B.0000-0001-8852-7306
Additional Information:© 1983 American Chemical Society. Received December 13, 1982. This work was supported by Grant GM-27681 from the National Institutes of Health and a National Research Service Award (GM-07616) to M.W.V.D. Contribution No. 6733 from the Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125.
Funding AgencyGrant Number
NIH Predoctoral FellowshipGM-07616
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Caltech Division of Chemistry and Chemical Engineering6733
Issue or Number:10
Record Number:CaltechAUTHORS:20160511-154956364
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Official Citation:Chromomycin, mithramycin, and olivomycin binding sites on heterogeneous DNA. Footprinting with methidiumpropyl-EDTA.cntdot.iron(II) Michael W. Van Dyke and Peter B. Dervan Biochemistry 1983 22 (10), 2373-2377 DOI: 10.1021/bi00279a011
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:67035
Deposited By: Victoria Brennan
Deposited On:19 May 2016 23:15
Last Modified:11 Nov 2021 00:26

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