Solution structures of 5-fluorouracil-substituted DNA and RNA decamer duplexes

Biochemistry. 1996 Oct 22;35(42):13597-608. doi: 10.1021/bi960535y.


The structures in solution of eight oligonucleotide duplexes each containing either zero, one, or two 5-fluorodeoxyuridine (FdUrd) or 5-fluorouridine (FUrd) nucleosides were determined by the combined use of NMR spectroscopy, restrained molecular dynamics, and full relaxation matrix refinement to determine how FdUrd and FUrd substitution affects the structure of duplex DNA and RNA and to establish whether structural differences due to FdUrd and FUrd substitution in nucleic acids may be responsible, in part, for the biological effects of the anticancer drug 5-fluorouracil (FUra). The nucleic acid directed effects of FUra include induction of single-strand breaks in duplex DNA and altered processing of pre-mRNA and rRNA. Four self-complementary oligodeoxyribonucleotide sequences were prepared and studied as duplexes in aqueous solution: (5' dGCGAAUUCGC)2, (5' dGCGAAUFCGC)2, (5' dGCGAAFUCGC)2, and (5' dGCGAAFFCGC)2. The corresponding oligoribonucleotide sequences (5' rGCGAAUUCGC)2, (5' rGCGAAUFCGC)2, (5' rGCGAAFUCGC)2, and (5' rGCGAAFFCGC)2 were also prepared and studied. The helical parameters for the structures of these eight duplexes were analyzed to determine how substitution of FdUrd and FUrd affects the three-dimensional structures of duplex DNA and RNA. FdUrd substitution affects the base roll angle at the site of FdUrd substitution, causing the helical axis of FdUrd-substituted DNA duplexes to be bent compared to the nonsubstituted duplex. A-FUrd base pairs show substantial RMS deviations from A-Urd base pairs in all three of the RNA duplexes substituted with FUrd. Bending of the helical axis due to FdUrd substitution may contribute to the occurrence of single-strand breaks in duplex DNA while the altered structures of A-FUrd base pairs may affect RNA-RNA and RNA-protein recognition.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Composition
  • DNA / chemistry*
  • Fluorouracil / chemistry*
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Molecular Structure
  • Nucleic Acid Conformation*
  • Oligodeoxyribonucleotides / chemistry
  • Oligoribonucleotides / chemistry
  • RNA, Double-Stranded / chemistry*


  • Oligodeoxyribonucleotides
  • Oligoribonucleotides
  • RNA, Double-Stranded
  • DNA
  • Fluorouracil