Conformations of nucleoside analogue 1-(2'-deoxy-beta-D-ribofuranosyl)-1,2,4-triazole-3-carboxamide in different DNA sequence contexts.
The concept of using a dynamic base-pairing nucleobase as a mode for degenerate recognition presents a unique challenge to analysis of DNA structure. Proton and phosphorus NMR studies are reported for two nine-residue DNA oligodeoxyribonucleotides, d(CATGGGTAC).d(GTACNCATG) (1) and d(CATGTGTAC).(GTACNCATG) (2), which contained 1-(2'-deoxy-beta-D-ribofuranosyl)-1,2,4-triazole-3-carboxamide (N) in the center of the helix at position 14. The duplexes were compared to the canonical Watson-Crick duplexes, d(CATGGGTAC).d(GTACCCATG) (3) and d(CATGTGTAC).d(GTACACATG) (4). Two-dimensional NOESY spectra of 1-4 in H(2)O and D(2)O solutions collected at 5 degrees C allowed assignment of the exchangeable and nonexchangeable protons for all four oligodeoxyribonucleotides. Thermodynamic and circular dichroism data indicated that 1-4 formed stable, B-form duplexes at 5 degrees C. Two-dimensional (1)H-(31)P correlation spectra indicated that there were minor perturbations in the backbone only near the site of the triazole base. Strong NOESY cross-peaks were observed between the H5 and H1' of N14 in 1 and, unexpectedly, 2, which indicated that, in both duplexes, N14 was in the syn(chi)() conformation about the glycosidic bond. NOESY spectra of 1 and 2 recorded in 95% H(2)O, 5% D(2)O indicated that the imino proton of the base opposite N14, G5, or T5, formed a weak hydrogen bond with N14. These conformations place the polar carboxamide functional group in the major groove with motional averaging on the intermediate time scale.
Klewer
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Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843-2128, USA.
Zhang
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Bergstrom
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Davisson
V J
VJ
LiWang
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AC
D000577:Amides / Q000737:chemistry; D020029:Base Pairing; D002942:Circular Dichroism; D006027:Glycosides / Q000737:chemistry; D006860:Hydrogen Bonding; D019906:Nuclear Magnetic Resonance, Biomolecular; D009690:Nucleic Acid Conformation; D009692:Nucleic Acid Heteroduplexes / Q000737:chemistry; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D010759:Phosphorus Isotopes; D011522:Protons; D012254:Ribavirin / Q000031:analogs & derivatives* / Q000737:chemistry*; D017422:Sequence Analysis, DNA; D013696:Temperature; D013816:Thermodynamics
D000577:Amides; D006027:Glycosides; D009692:Nucleic Acid Heteroduplexes; D009838:Oligodeoxyribonucleotides; D010759:Phosphorus Isotopes; D011522:Protons; D012254:Ribavirin; C026956:taribavirin