4'-Thio-β-D-oligoribonucleotides: Nuclease Resistance and Hydrogen Bonding Properties

Leydier, C.; Bellon, Laurent; Barascut, J. L.; Imbach, J.‐L.

doi:10.1080/15257779508012526

Cited by 15 publications

(23 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…4′-Thio-RNA binds more tightly to RNA than to DNA (19,20), consistent with the previous notion that RNA duplexes are more stable than RNA–DNA hybrids (21,22). The presence of sulfur at the 4′-position can be expected to change the pseudorotational equilibrium in the ribose moiety.…”

Section: Introductionsupporting

confidence: 89%

“…Incorporation of 4′-thio-U residues into RNA strands leads to enhanced thermal stability of duplexes between modified strands and RNA relative to the native counterparts (19,20). 4′-Thio-RNA binds more tightly to RNA than to DNA (19,20), consistent with the previous notion that RNA duplexes are more stable than RNA–DNA hybrids (21,22).…”

Section: Introductionmentioning

confidence: 99%

“…(27). Recent developments in the synthesis of 4′-thioribonucleosides have focused upon the synthesis of peracylated 4-thio- d -ribofuranose as a thiosugar precursor to glycosylation (20). This approach takes advantage of acyloxonium ion formation at C1 to give higher selectivity in generating the desired nucleoside β anomer product (28).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Syntheses of 4'-thioribonucleosides and thermodynamic stability and crystal structure of RNA oligomers with incorporated 4'-thiocytosine

Haeberli¹

2005

Nucleic Acids Research

View full text Add to dashboard Cite

A facile synthetic route for the 4′-thioribonucleoside building block 4′SN (N = U, C, A and G) with the ribose O4′ replaced by sulfur is presented. Conversion of l-lyxose to 1,5-di-O-acetyl-2,3-di-O-benzoyl-4-thio-d-ribofuranose was achieved via an efficient four-step synthesis with high yield. Conversion of the thiosugar into the four ribonucleoside phosphoramidite building blocks was accomplished with additional four steps in each case. Incorporation of 4′-thiocytidines into oligoribonucleotides improved the thermal stability of the corresponding duplexes by ∼1°C per modification, irrespective of whether the strand contained a single modification or a consecutive stretch of 4′SC residues. The gain in thermodynamic stability is comparable to that observed with oligoribonucleotides containing 2′-O-methylated residues. To establish potential conformational changes in RNA as a result of the 4′-thio modification and to better understand the origins of the observed stability changes, the crystal structure of the oligonucleotide 5′-r(CC4′SCCGGGG) was determined and analyzed using the previously solved structure of the native RNA octamer as a reference. The two 4′-thioriboses adopt conformations that are very similar to the C3′-endo pucker observed for the corresponding sugars in the native duplex. Subtle changes in the local geometry of the modified duplex are mostly due to the larger radius of sulfur compared to oxygen or appear to be lattice-induced. The significantly increased RNA affinity of 4′-thio-modified RNA relative to RNA, and the relatively minor conformational changes caused by the modification render this nucleic acid analog an interesting candidate for in vitro and in vivo applications, including use in RNA interference (RNAi), antisense, ribozyme, decoy and aptamer technologies.

show abstract

Section: Introductionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Syntheses of 4'-thioribonucleosides and thermodynamic stability and crystal structure of RNA oligomers with incorporated 4'-thiocytosine

Haeberli¹

2005

Nucleic Acids Research

View full text Add to dashboard Cite

show abstract

“…Alternative approaches to the generation of 4′-thio-RNA were published by Imbach and coworkers [93,94] and Matsuda and coworkers [95,96]. 4′-Thio-RNA displays enhanced nuclease resistance and also shows favorable pairing stability compared with RNA.…”

Section: 4′-thio-rnamentioning

confidence: 99%

Crystallographic Studies of Chemically Modified Nucleic Acids: A Backward Glance

Egli

Pallan

2010

Chemistry & Biodiversity

View full text Add to dashboard Cite

Chemically modified nucleic acids (CNAs) are widely explored as antisense oligonucleotide or small interfering RNA (siRNA) candidates for therapeutic applications. CNAs are also of interest in diagnostics, high-throughput genomics and target validation, nanotechnology and as model systems in investigations directed at a better understanding of the etiology of nucleic acid structure as well as the physical-chemical and pairing properties of DNA and RNA and for probing protein-nucleic acid interactions. In this article we review research conducted by our laboratory over the past two decades with a focus on crystal structure analyses of CNAs and artificial pairing systems. We highlight key insights into issues ranging from conformational distortions as a consequence of modification to the modulation of pairing strength and RNA affinity by stereoelectronic effects and hydration. Although crystal structures have only been determined for a subset of the large number of modifications that were synthesized and analyzed in the oligonucleotide context to date, they have yielded guiding principles for the design of new analogs with tailormade properties, including pairing specificity, nuclease resistance and cellular uptake. And, perhaps less obviously, crystallographic studies of CNAs and synthetic pairing systems have shed light on fundamental aspects of DNA and RNA structure and function that would not have been disclosed by investigations solely focused on the natural nucleic acids.

show abstract

“…-Together with collaborators at SIRNA Pharmaceuticals, we prepared all four 4'-thio phosphoramidite building blocks for solid-phase synthesis of modified RNAs [54]. Alternative approaches to the generation of 4'-thio-RNA were published by Imbach and co-workers [111] [112], and Matsuda and co-workers [113] [114]. 4'-Thio-RNA displays enhanced nuclease resistance and also shows favorable pairing stability compared with RNA.…”

Section: '-Arabinonucleic Acidmentioning

confidence: 99%

ChemInform Abstract: Crystallographic Studies of Chemically Modified Nucleic Acids: A Backward Glance

Egli

Pallan

2010

ChemInform

View full text Add to dashboard Cite

show abstract

4'-Thio-β-D-oligoribonucleotides: Nuclease Resistance and Hydrogen Bonding Properties

Cited by 15 publications

References 0 publications

Syntheses of 4'-thioribonucleosides and thermodynamic stability and crystal structure of RNA oligomers with incorporated 4'-thiocytosine

Syntheses of 4'-thioribonucleosides and thermodynamic stability and crystal structure of RNA oligomers with incorporated 4'-thiocytosine

Crystallographic Studies of Chemically Modified Nucleic Acids: A Backward Glance

ChemInform Abstract: Crystallographic Studies of Chemically Modified Nucleic Acids: A Backward Glance

Contact Info

Product

Resources

About