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. 1988 Mar 25;16(6):2489–2507. doi: 10.1093/nar/16.6.2489

Sequence-specific binding of luzopeptin to DNA.

K R Fox 1, H Davies 1, G R Adams 1, J Portugal 1, M J Waring 1
PMCID: PMC336385  PMID: 3362673

Abstract

We have examined the binding of luzopeptin, an antitumor antibiotic, to five DNA fragments of varying base composition. The drug forms a tight, possibly covalent, complex with the DNA causing a reduction in mobility on nondenaturing polyacrylamide gels and some smearing of the bands consistent with intramolecular cross-linking of DNA duplexes. DNAase I and micrococcal nuclease footprinting experiments suggest that the drug binds best to regions containing alternating A and T residues, although no consensus di- or trinucleotide sequence emerges. Binding to other sites is not excluded and at moderate ligand concentrations the DNA is almost totally protected from enzyme attack. Ligand-induced enhancement of DNAase I cleavage is observed at both AT and GC-rich regions. The sequence selectivity and characteristics of luzopeptin binding are quite different from those of echinomycin, a bifunctional intercalator of related structure.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Fox K. R., Waring M. J. DNA structural variations produced by actinomycin and distamycin as revealed by DNAase I footprinting. Nucleic Acids Res. 1984 Dec 21;12(24):9271–9285. doi: 10.1093/nar/12.24.9271. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Fox K. R., Waring M. J. Nucleotide sequence binding preferences of nogalamycin investigated by DNase I footprinting. Biochemistry. 1986 Jul 29;25(15):4349–4356. doi: 10.1021/bi00363a026. [DOI] [PubMed] [Google Scholar]
  3. Fox K. R., Waring M. J. The use of micrococcal nuclease as a probe for drug-binding sites on DNA. Biochim Biophys Acta. 1987 Jul 14;909(2):145–155. doi: 10.1016/0167-4781(87)90036-4. [DOI] [PubMed] [Google Scholar]
  4. Huang C. H., Mirabelli C. K., Mong S., Crooke S. T. Intermolecular cross-linking of DNA through bifunctional intercalation of an antitumor antibiotic, luzopeptin A (BBM-928A). Cancer Res. 1983 Jun;43(6):2718–2724. [PubMed] [Google Scholar]
  5. Huang C. H., Mong S., Crooke S. T. Interactions of a new antitumor antibiotic BBM-928A with deoxyribonucleic acid. Bifunctional intercalative binding studied by fluorometry and viscometry. Biochemistry. 1980 Nov 25;19(24):5537–5542. doi: 10.1021/bi00565a012. [DOI] [PubMed] [Google Scholar]
  6. Huang C. H., Prestayko A. W., Crooke S. T. Bifunctional intercalation of antitumor antibiotics BBM-928A and echinomycin with deoxyribonucleic acid. Effects of intercalation on deoxyribonucleic acid degradative activity of bleomycin and phleomycin. Biochemistry. 1982 Jul 20;21(15):3704–3710. doi: 10.1021/bi00258a028. [DOI] [PubMed] [Google Scholar]
  7. Low C. M., Drew H. R., Waring M. J. Sequence-specific binding of echinomycin to DNA: evidence for conformational changes affecting flanking sequences. Nucleic Acids Res. 1984 Jun 25;12(12):4865–4879. doi: 10.1093/nar/12.12.4865. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Low C. M., Fox K. R., Olsen R. K., Waring M. J. DNA sequence recognition by under-methylated analogues of triostin A. Nucleic Acids Res. 1986 Mar 11;14(5):2015–2033. doi: 10.1093/nar/14.5.2015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Ohkuma H., Sakai F., Nishiyama Y., Ohbayashi M., Imanishi H., Konishi M., Miyaki T., Koshiyama H., Kawaguchi H. BBM-928, a new antitumor antibiotic complex. I. Production, isolation, characterization and antitumor activity. J Antibiot (Tokyo) 1980 Oct;33(10):1087–1097. doi: 10.7164/antibiotics.33.1087. [DOI] [PubMed] [Google Scholar]
  10. Peterson R. C., Doering J. L., Brown D. D. Characterization of two xenopus somatic 5S DNAs and one minor oocyte-specific 5S DNA. Cell. 1980 May;20(1):131–141. doi: 10.1016/0092-8674(80)90241-x. [DOI] [PubMed] [Google Scholar]
  11. Ughetto G., Wang A. H., Quigley G. J., van der Marel G. A., van Boom J. H., Rich A. A comparison of the structure of echinomycin and triostin A complexed to a DNA fragment. Nucleic Acids Res. 1985 Apr 11;13(7):2305–2323. doi: 10.1093/nar/13.7.2305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Van Dyke M. M., Dervan P. B. Echinomycin binding sites on DNA. Science. 1984 Sep 14;225(4667):1122–1127. doi: 10.1126/science.6089341. [DOI] [PubMed] [Google Scholar]
  13. Wakelin S. P., Waring M. J. The binding of echinomycin to deoxyribonucleic acid. Biochem J. 1976 Sep 1;157(3):721–740. doi: 10.1042/bj1570721. [DOI] [PMC free article] [PubMed] [Google Scholar]

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