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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Single-strand DNA Binding of Actinomycin D with a Chromophore 2-Amino to 2-Hydroxyl Substitution

  • Yoo, Hoon (Department of Pharmacology and Dental Therapeutics, College of Dentistry, Chosun University) ;
  • Rill, Randolph L. (Department of Biomedical Sciences, The Florida State University)
  • Received : 2002.11.15
  • Accepted : 2003.01.24
  • Published : 2003.05.31
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Abstract

A modified actinomycin D was prepared with a hydroxyl group that replaced the amino group at the chromophore 2-position, a substitution known to strongly reduce affinity for double-stranded DNA. Interactions of the modified drug on single-stranded DNAs of the defined sequence were investigated. Competition assays showed that 2-hydroxyactinomycin D has low affinity for two oligonucleotides that have high affinities ($K_a\;=\;5-10{\times}10^6\;M^{-1}$ oligomer) for 7-aminoactinomycin D and actinomycin D. Primer extension inhibition assays performed on several single-stranded DNA templates totaling around 1000 nt in length detected a single high affinity site for 2-hydroxyactinomycin D, while many high affinity binding sites of unmodified actinomycin D were found on the same templates. The sequence selectivity of 2-hydroxyactinomycin D binding is unusually high and approximates the selectivity of restriction endonucleases. Binding appears to require a complex structure, including residues well removed from the polymerase pause site.

Keywords

References

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