The effect of two antipodal fluorine-induced sugar puckers on the conformation and stability of the Dickerson-Drew dodecamer duplex [d(CGCGAATTCGCG)]2.
UV thermal melting studies, CD and NMR spectroscopies were employed to assess the contribution of antipodal sugar conformations on the stability of the canonical B-DNA conformation of the Dickerson-Drew dodecamer duplex [[d(CGCGAATTCGCG)]2, (ODN 1)]. Different oligodeoxynucleotide versions of ODN 1 were synthesized with modified thymidine units favoring distinct sugar conformations by using a 3'- endo (north) 2'-fluoro-2'-deoxyribofuranosyl thymine (1) or a 2'- endo (south) 2'-fluoro-2'-deoxyarabinofuranosyl thymine (2). The results showed that two south thymidines greatly stabilized the double helix, whereas two north thymidines destabilized it by inducing a more A-like conformation in the middle of the duplex. Use of combinations of north and south thymidine conformers in the same oligo destabilized the double helix even further, but without inducing a conformational change. The critical length for establishing a detectable A-like conformation in the middle of a B-DNA ODN appears to be 4 bp. Our results suggest that manipulation of the conformation of DNA in a sequence-independent manner is possible.
Ikeda
H
H
Laboratory of Medicinal Chemistry, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Fernandez
R
R
Wilk
A
A
Barchi
J J
JJ
Huang
X
X
Marquez
V E
VE
D004247:DNA / Q000737:chemistry*; D005461:Fluorine; D006358:Hot Temperature; D019906:Nuclear Magnetic Resonance, Biomolecular; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D013936:Thymidine / Q000031:analogs & derivatives*
D009838:Oligodeoxyribonucleotides; D005461:Fluorine; D004247:DNA; D013936:Thymidine