2dpc: Difference between revisions

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[[Image:2dpc.gif|left|200px]]
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[[Image:2dpc.png|left|200px]]


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{{STRUCTURE_2dpc|  PDB=2dpc  |  SCENE=  }}  
{{STRUCTURE_2dpc|  PDB=2dpc  |  SCENE=  }}  


'''Crystal Structure of d(CGCGAATXCGCG) Where X is 5-(N-aminohexyl)carbamoyl-2'-O-methyluridine'''
===Crystal Structure of d(CGCGAATXCGCG) Where X is 5-(N-aminohexyl)carbamoyl-2'-O-methyluridine===




==Overview==
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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.
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{{ABSTRACT_PUBMED_17341465}}


==About this Structure==
==About this Structure==
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[[Category: B-dna]]
[[Category: B-dna]]
[[Category: Modified nucleotide]]
[[Category: Modified nucleotide]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 05:15:30 2008''

Revision as of 02:15, 28 July 2008

File:2dpc.png

Template:STRUCTURE 2dpc

Crystal Structure of d(CGCGAATXCGCG) Where X is 5-(N-aminohexyl)carbamoyl-2'-O-methyluridine

Template:ABSTRACT PUBMED 17341465

About this Structure

2DPC is a Single protein structure. 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;35(6):1969-77. Epub 2007 Mar 6. PMID:17341465

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