Conformations of Nucleoside Analogue 1-(2'-Deoxy--D-ribofuranosyl)-1,2,4-triazole-3-carboxamid

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• 作者：Douglas A. Klewer ; Peiming Zhang ; Donald E. Bergstrom ; V. Jo Davisson ; and Andy C. LiWang
• 刊名：Biochemistry
• 出版年：2001
• 出版时间：February 13, 2001
• 年：2001
• 卷：40
• 期：6
• 页码：1518 - 1527
• 全文大小：192K
• 年卷期：v.40,no.6(February 13, 2001)
• ISSN：1520-4995

文摘

The concept of using a dynamic base-pairing nucleobase as a mode for degenerate recognitionpresents a unique challenge to analysis of DNA structure. Proton and phosphorus NMR studies are reportedfor two nine-residue DNA oligodeoxyribonucleotides, d(CATGGGTAC)·d(GTACNCATG) (1) andd(CATGTGTAC)·(GTACNCATG) (2), which contained 1-(2'-deoxy-mages/gifchars/beta2.gif" BORDER=0 ALIGN="middle">-D-ribofuranosyl)-1,2,4-triazole-3-carboxamide (N) in the center of the helix at position 14. The duplexes were compared to the canonicalWatson-Crick duplexes, d(CATGGGTAC)·d(GTACCCATG) (3) and d(CATGTGTAC)·d(GTACACATG)(4). Two-dimensional NOESY spectra of 1-4 in H₂O and D₂O solutions collected at 5 mages/entities/deg.gif">C allowedassignment 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 mages/entities/deg.gif">C.Two-dimensional ¹H-³¹P correlation spectra indicated that there were minor perturbations in the backboneonly near the site of the triazole base. Strong NOESY cross-peaks were observed between the H5 andH1' of N14 in 1 and, unexpectedly, 2, which indicated that, in both duplexes, N14 was in the syn_{mages/gifchars/chi.gif" BORDER=0 >}conformation about the glycosidic bond. NOESY spectra of 1 and 2 recorded in 95% H₂O, 5% D₂Oindicated that the imino proton of the base opposite N14, G5, or T5, formed a weak hydrogen bond withN14. These conformations place the polar carboxamide functional group in the major groove with motionalaveraging on the intermediate time scale.