Structural and dynamic properties of a fluorouracil-adenine base pair in DNA studied by proton NMR.
An oligodeoxynucleotide duplex containing the chemotherapeutic agent 5-fluorouracil (FU) has been constructed by solid phase phosphotriester synthesis and has been studied in solution by proton NMR. In this study, we provide the first structural characterization of a DNA complex containing a FU.A base pair. It has been determined that the 7-mer duplex containing a central FU.A base pair adopts a normal right-handed configuration and the A residue in the FU.A pair is oriented in the normal anticonfiguration giving a Watson-Crick base pair. The significant difference between T.A and FU.A base pairs is dynamic, not structural: the FU.A base pair opens faster than normal base pairs in the oligonucleotide studied. We provide evidence that the FU.A base pair has a significantly enhanced opening rate resulting form decreased stacking of the 5-fluorouracil residue and not from the enhanced acidity of the 5'-fluorouracil imino proton.
Sowers
L C
LC
Department of Biological Sciences, University of Southern California, Los Angeles 90089-1481.
Eritja
R
R
Kaplan
B E
BE
Goodman
M F
MF
Fazakerley
G V
GV
D000225:Adenine; D004247:DNA; D005472:Fluorouracil; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D009690:Nucleic Acid Conformation
D004247:DNA; D000225:Adenine; D005472:Fluorouracil