Copper(I)-bleomycin

Structurally unique complex that mediates oxidative DNA strand scission

Guy M. Ehrenfeld, Luis O. Rodriguez, Sidney Hecht, Cynthia Chang, Vladimir J. Basus, Norman J. Oppenheimer

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

Copper(I)-bleomycin [Cu(I)·BLM] was characterized in detail by 13C and 1H NMR. Unequivocal chemical shift assignments for Cu(I)·BLM and Cu(I)·BLM·CO were made by two-dimensional 1H-13C correlated spectroscopy and by utilizing the observation that Cu(I)·BLM was in rapid equilibrium with Cu(I) and metal-free bleomycin, such that individual resonances in the spectra of BLM and Cu(I)·BLM could be correlated. The binding of Cu(I) by bleomycin involves the β-aminoalaninamide and pyrimidinyl moieties, and possibly the imidazole, but not Nα of β-hydroxyhistidine. Although no DNA strand scission by Cu(II)·BLM could be demonstrated in the absence of dithiothreitol, in the presence of this reducing agent substantial degradation of [3H]DNA was observed, as was strand scission of cccDNA. DNA degradation by Cu(I)·BLM was shown not to depend on contaminating Fe(II) and not to result in the formation of thymine propenal; the probable reason(s) for the lack of observed DNA degradation in earlier studies employing Cu(II)·BLM and dithiothreitol was (were) also identified. DNA strand scission was also noted under anaerobic conditions when Cu(II)·BLM and iodosobenzene were employed. If it is assumed that the mechanism of DNA degradation in this case is the same as that under aerobic conditions (i.e., with Cu(I)·BLM + O2 in the presence of dithiothreitol), then Cu·BLM must be capable of functioning as a monooxygenase in its degradation of DNA.

Original languageEnglish (US)
Pages (from-to)81-92
Number of pages12
JournalBiochemistry
Volume24
Issue number1
StatePublished - 1985
Externally publishedYes

Fingerprint

Bleomycin
Copper
DNA
Dithiothreitol
Degradation
Reducing Agents
Chemical shift
Mixed Function Oxygenases
copper bleomycin
Spectrum Analysis
Metals
Nuclear magnetic resonance
Spectroscopy

ASJC Scopus subject areas

  • Biochemistry

Cite this

Ehrenfeld, G. M., Rodriguez, L. O., Hecht, S., Chang, C., Basus, V. J., & Oppenheimer, N. J. (1985). Copper(I)-bleomycin: Structurally unique complex that mediates oxidative DNA strand scission. Biochemistry, 24(1), 81-92.

Copper(I)-bleomycin : Structurally unique complex that mediates oxidative DNA strand scission. / Ehrenfeld, Guy M.; Rodriguez, Luis O.; Hecht, Sidney; Chang, Cynthia; Basus, Vladimir J.; Oppenheimer, Norman J.

In: Biochemistry, Vol. 24, No. 1, 1985, p. 81-92.

Research output: Contribution to journalArticle

Ehrenfeld, GM, Rodriguez, LO, Hecht, S, Chang, C, Basus, VJ & Oppenheimer, NJ 1985, 'Copper(I)-bleomycin: Structurally unique complex that mediates oxidative DNA strand scission', Biochemistry, vol. 24, no. 1, pp. 81-92.
Ehrenfeld GM, Rodriguez LO, Hecht S, Chang C, Basus VJ, Oppenheimer NJ. Copper(I)-bleomycin: Structurally unique complex that mediates oxidative DNA strand scission. Biochemistry. 1985;24(1):81-92.
Ehrenfeld, Guy M. ; Rodriguez, Luis O. ; Hecht, Sidney ; Chang, Cynthia ; Basus, Vladimir J. ; Oppenheimer, Norman J. / Copper(I)-bleomycin : Structurally unique complex that mediates oxidative DNA strand scission. In: Biochemistry. 1985 ; Vol. 24, No. 1. pp. 81-92.
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