title: The effect of two antipodal fluorine-induced sugar puckers on the conformation and stability of the Dickerson-Drew dodecamer duplex [d(CGCGAATTCGCG)]2.
abstract: 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.
authors.affiliation: Laboratory of Medicinal Chemistry, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: H
authors.initials: H
authors.lastname: Ikeda
authors.forename: R
authors.initials: R
authors.lastname: Fernandez
authors.forename: A
authors.initials: A
authors.lastname: Wilk
authors.forename: J J
authors.initials: JJ
authors.lastname: Barchi
authors.forename: X
authors.initials: X
authors.lastname: Huang
authors.forename: V E
authors.initials: VE
authors.lastname: Marquez
mesh_terms: 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*
chemical_list: D009838:Oligodeoxyribonucleotides; D005461:Fluorine; D004247:DNA; D013936:Thymidine