High Fidelity Base Pairing at the 3′-Terminus.
Binding target strands with single base selectivity at a terminal position is difficult with natural DNA or RNA hybridization probes. Nature uses a degenerate genetic code that is based on RNA:RNA codon:anticodon duplexes tolerating wobble base pairs at the terminus. The importance of short RNA stra...
| Publicado en: | Journal of the American Chemical Society Vol. 131; no. 35; pp. 12671 - 12682 |
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| Autores principales: | , |
| Formato: | Artículo |
| Publicado: |
American Chemical Society
9/9/2009
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=hlh&AN=44475498&site=ehost-live header: @attributes: shortDbName: hlh uiTerm: 44475498 longDbName: Humanities International Complete uiTag: AN controlInfo: bkinfo: jinfo: jid: 00027863 ACS jtl: Journal of the American Chemical Society issn: 00027863 maglogo: N pubinfo: dt: 9/9/2009 vid: 131 iid: 35 pid: 997 pub: American Chemical Society artinfo: ui: 44475498 10.1021/ja9033654 ppf: 12671 ppct: 11 formats: tig: atl: High Fidelity Base Pairing at the 3′-Terminus. aug: au: Patra, Amritraj Richert, Clemens affil: University of Karlsruhe University of Stuttgart su: Nucleic acid hybridization Genetic code Hydrogen bonding Molecular dynamics sug: subj: Nucleic acid hybridization Genetic code Hydrogen bonding Molecular dynamics ab: Binding target strands with single base selectivity at a terminal position is difficult with natural DNA or RNA hybridization probes. Nature uses a degenerate genetic code that is based on RNA:RNA codon:anticodon duplexes tolerating wobble base pairs at the terminus. The importance of short RNA strands in regulatory processes in the cell make it desirable to develop receptor-like approaches for high fidelity binding, even at the very 3′-terminus of a probe. Here, we report the three-dimensional structure of a DNA duplex with a 3′-terminal 2′-anthraquinoylamido-2′-deoxyuridine (Uaq) residue that was solved by NMR and restrained molecular dynamics. The Uaq residue binds the 5′-terminus of the target strand through a combination of π-stacking, hydrogen bonding, and interactions in the minor groove. The acylated aminonucleoside is the best molecular cap for 3′-termini reported to date. The Uaq motif assists binding of DNA strands, but is particularly effective in enhancing the affinity for RNA target strands, with a ΔT in the UV melting point of up to +18.2°C per residue. Increased base pairing selectivity is induced for all sequence motifs tested, even in cases where unmodified duplexes show no preference for the canonical base pair at all. A single mismatched nucleobase facing the 3′-terminus gives ΔΔT values as large as -23.9 °C (RNA) or -29.5 °C (DNA). The 5′-phosphoramidite of the Uaq cap reported here allows for routine incorporation during automated syntheses. pubtype: Academic Journal doctype: Article src: R language: English refInfo: copyright: @attributes: flag: Y dt: @attributes: year: 2009 holdings: @attributes: islocal: N |
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