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Nucleic Acids Res. Mar 25, 1988; 16(6): 2489–2507.
PMCID: PMC336385

Sequence-specific binding of luzopeptin to DNA.


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

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  • Huang CH, Mong S, Crooke ST. 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. [PubMed]
  • 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. [PubMed]
  • Huang CH, Prestayko AW, Crooke ST. 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. [PubMed]
  • Huang CH, Mirabelli CK, Mong S, Crooke ST. 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]
  • Ughetto G, Wang AH, Quigley GJ, van der Marel GA, van Boom JH, 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. [PMC free article] [PubMed]
  • Wakelin SP, Waring MJ. The binding of echinomycin to deoxyribonucleic acid. Biochem J. 1976 Sep 1;157(3):721–740. [PMC free article] [PubMed]
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  • Low CM, Fox KR, Olsen RK, Waring MJ. DNA sequence recognition by under-methylated analogues of triostin A. Nucleic Acids Res. 1986 Mar 11;14(5):2015–2033. [PMC free article] [PubMed]
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