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1ac3

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(New page: 200px<br /><applet load="1ac3" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ac3" /> '''SOLUTION STRUCTURE OF AN RNA-DNA HYBRID DUPL...)
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Revision as of 20:32, 24 November 2007

Image:1ac3.gif

1ac3

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SOLUTION STRUCTURE OF AN RNA-DNA HYBRID DUPLEX CONTAINING A 3'-THIOFORMACETAL LINKER AND AN RNA A-TRACT, NMR, 8 STRUCTURES

Overview

Neutral and achiral backbone linkers are promising replacements for the, phosphodiester linkages of antisense oligonucleotides that target mRNA, sequences. Results are presented here for the solution structure, elucidation by NMR of an RNA x DNA hybrid duplex, r(GCGCAAAACGCG) x, d(CGCGTT-SCH2O-TTGCGC) (designated RIII), containing a 3'-thioformacetal, (3'-TFMA) backbone substitution in the DNA strand. The 3'-thioformacetal, linker can be accommodated in the hybrid duplex in a conformation that is, drastically different from its form in a DNA x DNA duplex but close to, that of the canonical A-form helix, reflecting the sequence requirement, for hybridization. While the global features of RIII are similar to what, are described in the literature, the 3'-TFMA modification drives sugar, puckers of the adjacent residues to more C3'-endo-like conformations and, causes distortions in related twist angles and helical rises. The helical, conformation analyses of each of the two strands and the hybrid duplex, enable a clear account of the conformational variability of both the DNA, and RNA strands. The A-tract in the RNA strand features an overall, straight helix and a more prominent bend at the 3'-end CG step. The, structure of RIII provides a structural basis for the improved thermal, stability of RIII compared to the corresponding DNA x DNA duplex and, insights into the factors that are important concerns for the design of, new, effective antisense oligonucleotides.

About this Structure

1AC3 is a Single protein structure of sequence from [1]. Full crystallographic information is available from OCA.

Reference

Solution structure of an RNA x DNA hybrid duplex containing a 3'-thioformacetal linker and an RNA A-tract., Cross CW, Rice JS, Gao X, Biochemistry. 1997 Apr 8;36(14):4096-107. PMID:9100003

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