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| | {{STRUCTURE_2axb| PDB=2axb | SCENE= }} | | {{STRUCTURE_2axb| PDB=2axb | SCENE= }} |
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| - | '''Crystal Structure Analysis Of A 2-O-[2-(methoxy)ethyl]-2-thiothymidine Modified Oligodeoxynucleotide Duplex'''
| + | ===Crystal Structure Analysis Of A 2-O-[2-(methoxy)ethyl]-2-thiothymidine Modified Oligodeoxynucleotide Duplex=== |
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| - | ==Overview==
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| - | Substitution of oxygen atoms by sulfur at various locations in the nucleic acid framework has led to analogs such as the DNA phosphorothioates and 4'-thio RNA. The phosphorothioates are excellent mimics of DNA, exhibit increased resistance to nuclease degradation compared with the natural counterpart, and have been widely used as first-generation antisense nucleic acid analogs for applications in vitro and in vivo. The 4'-thio RNA analog exhibits significantly enhanced RNA affinity compared with RNA, and shows potential for incorporation into siRNAs. 2-Thiouridine (s2U) and 5-methyl-2-thiouridine (m5s2U) are natural nucleotide analogs. s2U in tRNA confers greater specificity of codon-anticodon interactions by discriminating more strongly between A and G compared with U. 2-Thio modification preorganizes the ribose and 2'-deoxyribose sugars for a C3'-endo conformation, and stabilizes heteroduplexes composed of modified DNA and complementary RNA. Combination of the 2-thio and sugar 2'-O-modifications has been demonstrated to boost both thermodynamic stability and nuclease resistance. Using the 2'-O-[2-(methoxy)ethyl]-2-thiothymidine (m5s2Umoe) analog, we have investigated the consequences of the replacement of the 2-oxygen by sulfur for base-pair geometry and duplex conformation. The crystal structure of the A-form DNA duplex with sequence GCGTAT*ACGC (T* = m5s2Umoe) was determined at high resolution and compared with the structure of the corresponding duplex with T* = m5Umoe. Notable changes as a result of the incorporation of sulfur concern the base-pair parameter 'opening', an improvement of stacking in the vicinity of modified nucleotides as measured by base overlap, and a van der Waals interaction between sulfur atoms from adjacent m5s2Umoe residues in the minor groove. The structural data indicate only minor adjustments in the water structure as a result of the presence of sulfur. The observed small structural perturbations combined with the favorable consequences for pairing stability and nuclease resistance (when combined with 2'-O-modification) render 2-thiouracil-modified RNA a promising candidate for applications in RNAi.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_16170156}}, adds the Publication Abstract to the page |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Rajeev, K G.]] | | [[Category: Rajeev, K G.]] |
| | [[Category: Dna]] | | [[Category: Dna]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 19:35:14 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 14:00:08 2008'' |
Revision as of 11:00, 29 July 2008
Template:STRUCTURE 2axb
Crystal Structure Analysis Of A 2-O-[2-(methoxy)ethyl]-2-thiothymidine Modified Oligodeoxynucleotide Duplex
Template:ABSTRACT PUBMED 16170156
About this Structure
Full crystallographic information is available from OCA.
Reference
Stabilizing contributions of sulfur-modified nucleotides: crystal structure of a DNA duplex with 2'-O-[2-(methoxy)ethyl]-2-thiothymidines., Diop-Frimpong B, Prakash TP, Rajeev KG, Manoharan M, Egli M, Nucleic Acids Res. 2005 Sep 16;33(16):5297-307. Print 2005. PMID:16170156
Page seeded by OCA on Tue Jul 29 14:00:08 2008
