Application of 13C(omega 1)-half-filtered [1H,1H]-NOESY for studies of a complex formed between DNA and a 13C-labeled minor-groove-binding drug.
The complex formed between the anticancer drug 4-[p-[p-(4-quinolylamino)benzamido]anilino]pyridine (SN 6999) and the decadeoxyribonucleoside nonaphosphate d-(GCATTAATGC)2 was investigated using two-dimensional nuclear Overhauser enhancement spectroscopy (NOESY) with a 13C(omega 1)-half-filter. The two quaternary methyl groups in SN 6999 had been labeled with 13C for these experiments. The simplified subspectra of [1H,1H]-NOESY obtained with this procedure greatly facilitate the identification and assignment of intermolecular NOEs. Quite generally, the combined use of isotope labeling and heteronuclear filters in [1H,1H]-NOESY provides an improved experimental basis for structural studies of drug/DNA complexes.
Leupin
W
W
Institut für Molekularbiologie und Biophysik, ETH-Hönggerberg, Zürich, Switzerland.
Otting
G
G
Amacker
H
H
Wüthrich
K
K
D001483:Base Sequence; D004247:DNA / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000378:metabolism; D011806:Quinolinium Compounds / Q000378:metabolism*
D009838:Oligodeoxyribonucleotides; D011806:Quinolinium Compounds; C062476:SN 6999; D004247:DNA