2dqq

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Revision as of 09:18, 23 January 2008

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spinqualitylabelsall models 2dqq, resolution 2.0Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal Structure of d(CXCTXCTTC):r(gaagaagag) Where X is 5-(N-aminohexyl)carbamoyl-2'-O-methyluridine

Overview

Oligonucleotides containing 5-(N-aminohexyl)carbamoyl-modified uracils, have promising features for applications as antigene and antisense, therapies. Relative to unmodified DNA, oligonucleotides containing, 5-(N-aminohexyl)carbamoyl-2'-deoxyuridine ((N)U) or, 5-(N-aminohexyl)carbamoyl-2'-O-methyluridine ((N)U(m)), respectively, exhibit increased binding affinity for DNA and RNA, and enhanced nuclease, resistance. To understand the structural implications of (N)U and (N)U(m), substitutions, we have determined the X-ray crystal structures of DNA:DNA, duplexes containing either (N)U or (N)U(m) and of DNA:RNA hybrid duplexes, containing (N)U(m). The aminohexyl chains are fixed in the major groove, through hydrogen bonds between the carbamoyl amino groups and the uracil, O4 atoms. The terminal ammonium cations on these chains could interact, with the phosphate oxygen anions of the residues in the target strands., These interactions partly account for the increased target binding, affinity and nuclease resistance. In contrast to (N)U, (N)U(m) decreases, DNA binding affinity. This could be explained by the drastic changes in, sugar puckering and in the minor groove widths and hydration structures, seen in the (N)U(m) containing DNA:DNA duplex structure. The conformation, of (N)U(m), however, is compatible with the preferred conformation in, DNA:RNA hybrid duplexes. Furthermore, the ability of (N)U(m) to render the, duplexes with altered minor grooves may increase nuclease resistance and, elicit RNase H activity.

About this Structure

2DQQ is a Protein complex structure of sequences from [1] with as ligand. Full crystallographic information is available from OCA.

Reference

Crystal structures of DNA:DNA and DNA:RNA duplexes containing 5-(N-aminohexyl)carbamoyl-modified uracils reveal the basis for properties as antigene and antisense molecules., Juan EC, Kondo J, Kurihara T, Ito T, Ueno Y, Matsuda A, Takenaka A, Nucleic Acids Res. 2007 Mar 6;. PMID:17341465

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