The reaction of anthramycin with DNA. Proton and carbon nuclear magnetic resonance studies on the structure of the anthramycin-DNA adduct

Academic Article

Abstract

  • Nuclear magnetic resonance techniques are used to confirm the points of attachment of anthramycin to DNA. Using 13C NMR spectroscopy, the C-11 resonance of anthramycin is shown to undergo a 16-ppm upfield shift upon formation of a covalent bond with DNA, indicative of an animal linkage at that position. The site of attachment on the DNA is determined using the self-complementary oligodeoxyribonucleotide d-(ApTpGpCpApT) as a DNA model. Proton NMR, both in H2O and D2O solutions, provides a direct characterization of the anthramycin-oligonucleotide adduct. Upon covalent attachment to the duplex, a loss in the helical symmetry is observed, resulting in a doubling of several of the oligonucleotide resonances. Examination of the data confirms that the point of attachment of the anthramycin to the d-(ApTpGpCpApT) is at the guanine-NH2-position, consistent with the model proposed by Hurley and Petrusek (Hurley, L.H., and Petrusek, R.L. (1979) Nature (Lond.) 282, 529-531) and Petrusek et al. (Petrusek, R.L., Anderson, G.L., Garner, T.F., Fannin, Q.L., Kaplan, D.J., Zimmer, S.G., and Hurley, L.H. (1981) Biochemistry 20, 1111-1119).
  • Published In

    Author List

  • Graves DE; Pattaroni C; Krishnan BS; Ostrander JM; Hurley LH; Krugh TR
  • Start Page

  • 8202
  • End Page

  • 8209
  • Volume

  • 259
  • Issue

  • 13