A novel DNA structure induced by the anticancer bisplatinum compound crosslinked to a GpC site in DNA.
The bifunctional platinum compound, [(trans-PtCI(NH)3)2)2(H2N(CH2)4NH2)]2+, forms a stable adduct with the self-complementary DNA oligomer CATGCATG, with the two platinum atoms coordinated at the N7 positions of the two symmetrical G4 nucleotides. The NMR-derived structure shows that the DNA octamer forms a novel hairpin structure with the platinated G4 residue adopting a syn conformation and the guanine base in the minor groove. Two such hairpins stack end-over-end and are linked together by the butanediamine tether to form a dumbbell structure. Such unusual structural distortion is different from that of the anticancer drug cisplatin-DNA adduct and may provide clues to explain the distinct biological activities of the two compounds.
Yang
D
D
Biophysics Division, University of Illinois at Urbana-Champaign 61801, USA.
van Boom
S S
SS
Reedijk
J
J
van Boom
J H
JH
Farrell
N
N
Wang
A H
AH
D000970:Antineoplastic Agents / Q000737:chemistry*; D004247:DNA / Q000737:chemistry* / Q000648:ultrastructure; D018736:DNA Adducts / Q000737:chemistry*; D004249:DNA Damage; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009944:Organoplatinum Compounds / Q000737:chemistry*
D000970:Antineoplastic Agents; D018736:DNA Adducts; D009944:Organoplatinum Compounds; D004247:DNA