Two-dimensional nuclear magnetic resonance studies of an intercalation complex between the novel semisynthetic anthracycline 3'-deamino-3'-(2-methoxy-4-morpholinyl)-doxorubicin and the hexanucleotide duplex d(CGTACG).
The complex of the hexanucleotide duplex d(CGTACG) and the antitumor drug 3'-(2-methoxy-4-morpholinyl)-doxorubicin was investigated by two-dimensional 1H nuclear magnetic resonance spectroscopy. After complete assignment of the non-exchanging DNA protons and nearly all drug protons, eight nuclear Overhauser enhancement interactions between drug and DNA were measured at short mixing times. A model was built which shows that the overall structure is very similar to the related daunomycin complex, with the new morpholinyl-substituent extending further into the minor groove of the DNA double helix. The structural information is used for the discussion of the possible formation of DNA-adducts by the new anticancer drug.
Odefey
C
C
Department of Toxicology, University Medical School, Hamburg, Germany.
Westendorf
J
J
Dieckmann
T
T
Oschkinat
H
H
D000903:Antibiotics, Antineoplastic / Q000737:chemistry; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000737:chemistry; D007364:Intercalating Agents / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008956:Models, Chemical; D009841:Oligonucleotides / Q000737:chemistry*; D013057:Spectrum Analysis / Q000379:methods; D013329:Structure-Activity Relationship
D000903:Antibiotics, Antineoplastic; D007364:Intercalating Agents; D009841:Oligonucleotides; C066998:methoxy-morpholinyl-doxorubicin; D004317:Doxorubicin