NMR studies of the interaction of the antibiotic nogalamycin with the hexadeoxyribonucleotide duplex d(5'-GCATGC)/sub 2/
/sup 1/H resonance assignments in the NMR spectra of the self-complementary hexadeoxyribonucleoside pentaphosphate d(5'-GCATGC)/sub 2/ and its complex with the antibiotic nogalamycin, together with interproton distance constraints obtained from two-dimensional nuclear Overhauser effect (NOE) spectra, have enabled the authors to characterize the three-dimensional structure of these species in solution. In the complex described, two drug molecules are bound per duplex, in each of two equivalent binding sites, with full retention of the dyad symmetry. Twenty-eight NOE distance constraints between antibiotic and nucleotide protons define the position and orientation of the bound drug molecule. Nogalamycin intercalates at the 5'-CA and 5'-TG steps with the major axis of the anthracycline chromophore aligned approximately at right angles to the major axes of the base pairs. The nogalose sugar occupies the minor groove of the helix and makes many contacts with the deoxyribose moieties of three nucleotides along one strand of the duplex in the 5'-TGC segment. The charged dimethylamino group and hydroxyl functions of the bicyclic sugar lie in the major groove juxtaposed to the guanine base, the bridging atoms of the bicyclic sugar making contacts with the methyl group of the thymine. Thus the antibiotic is not symmetrically disposed in the intercalation site but is in close contact in both grooves with atoms comprising the 5'-TGC strand. The intercalation cavity is wedge-shaped, the major axes of the base pairs forming the site being tilted with respect to one another.
- Research Organization:
- Peter MacCallum Cancer Institute, Melbourne (Australia)
- OSTI ID:
- 6904783
- Journal Information:
- Biochemistry; (United States), Vol. 27:12
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
ANTIBIOTICS
CONFIGURATION INTERACTION
NUCLEAR MAGNETIC RESONANCE
OLIGONUCLEOTIDES
HEAVY WATER
NMR SPECTRA
OVERHAUSER EFFECT
PHOSPHORUS 31
PROTONS
ANTI-INFECTIVE AGENTS
BARYONS
DRUGS
ELEMENTARY PARTICLES
FERMIONS
HADRONS
HYDROGEN COMPOUNDS
ISOTOPES
LIGHT NUCLEI
MAGNETIC RESONANCE
NUCLEI
NUCLEIC ACIDS
NUCLEONS
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
OXYGEN COMPOUNDS
PHOSPHORUS ISOTOPES
RESONANCE
SPECTRA
STABLE ISOTOPES
WATER
550601* - Medicine- Unsealed Radionuclides in Diagnostics