Antisense Oligonucleotides

Mesmaeker, Alain De; Haener, Robert; Martin, Pierre; Moser, Heinz

doi:10.1021/ar00057a002

Cited by 425 publications

(245 citation statements)

References 27 publications

Supporting

Mentioning

234

Contrasting

Unclassified

Order By: Relevance

“…Furthermore, 2 0 -modifications is known to increase the stability against chemical and enzymatic degradation. [122][123][124][125] Very recently, Lauridsen et al reported a review article describing the enzymatic recognition capabilities of various 2 0 -modified nucleotides. 126 Stemming from their initial enzymatic recognition studies, 2 0 -amino pyrimidines, 2 0 -fluoro pyrimidines and 2 0 -O-Methyl nucleotides have been successfully applied in aptamer development by conventional SELEX-based methodologies.…”

Section: Chemically Modified Aptamer-oligonucleotide Chimeramentioning

confidence: 99%

Smart functional nucleic acid chimeras: Enabling tissue specific RNA targeting therapy

et al. 2015

View full text Add to dashboard Cite

Section: Chemically Modified Aptamer-oligonucleotide Chimeramentioning

confidence: 99%

Smart functional nucleic acid chimeras: Enabling tissue specific RNA targeting therapy

et al. 2015

View full text Add to dashboard Cite

“…The structure of the duplex with the same sequence containing a single 2′- O -[2-(methoxy)ethyl]-thymidine per strand (5′-GCGTA(m 5 Umoe)ACGC) had previously been determined at a similar resolution and was used as the reference (20). The 2′- O -MOE RNA analog is a promising second-generation antisense modification that leads to significant gains in RNA affinity as well as enhanced nuclease resistance compared with DNA or PS-DNA (21,22). The roles of conformational preorganization, stereoelectronic effects and hydration in the stability increases afforded by the 2′- O -MOE modification have been studied extensively using crystallographic data obtained for partially (20) and all-2′- O -modified duplexes (23).…”

Section: Introductionmentioning

confidence: 99%

Stabilizing contributions of sulfur-modified nucleotides: crystal structure of a DNA duplex with 2'-O-[2-(methoxy)ethyl]-2-thiothymidines

Diop-Frimpong

Prakash²,

Rajeev³

et al. 2005

Nucleic Acids Research

View full text Add to dashboard Cite

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.

show abstract

“…Both effects, directed to viral sequences within double-stranded DNA or single-stranded mRNA, allow regulation of gene expression at the stage of transcription (antigene strategy) 10 or translation (antisense strategy). 11 Clearly, highly reactive metal complexes containing reactive ligands should be able to give more desirable therapeutic effect because of irreversible covalent binding to DNA. 12 This has been proven for a wide range of functional metal complexes, such as cisplatin 13 and its ruthenium analogs 14 , cis-and trans-Ru II Cl 2 (DMSO) 4 , Ru II (bpy) 2 Cl 2 , Ru III (tpy)Cl 3 , [Ru II (NH 3 ) 5 Cl]Cl (bpy = 2,2'-bipyridine, tpy = 2,2':6',2''-terpyridine), which showed antitumor activity and pronounced antimetastatic properties.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of the DNA−[Ru(tpy)(dppz)(CH₃CN)]²⁺ Conjugates and Their Photo Cross-Linking Studies with the Complementary DNA Strand

2002

View full text Add to dashboard Cite

We here report our studies on the conjugation of photoreactive Ru 2+ complex to oligonucleotides (ODNs), which give stable duplex with the complementary target DNA strand. These functionalized DNA duplexes bearing photoreactive Ru 2+ complex can be specifically photolyzed to give the reactive aqua derivative, [Ru(tpy)(dppz)(H 2 O)] 2+ -ODN, in situ, which successfully cross-links to give photoproduct(s) with the target DNA strand in a sequence specific manner. Thus, the stable precursor of aqua-ruthenium complex, monofunctional polypyridyl ruthenium complex:[Ru(tpy)(dppz)(CH 3 CN)] 2+ (tpy = 2,2':6',2''-terpyridine, dppz = dipyrido[3,2-a:2',3'-c]phenazine), has been site-specifically tethered to ODN, for the first time, both by solid phase synthesis and post- Table 1). This shows that with the rigidly packed structure, as in the duplex with middle-Ru 2+ ODN, the metal center flexibility is considerably reduced, and consequently the accessibility of target G residue by the aquaruthunium moiety becomes severely restricted, which results in a poor yield in the cross-coupling reaction. The crosslinked product was characterized by PAGE, followed by MALDI-TOF MS.

show abstract

Antisense Oligonucleotides

Cited by 425 publications

References 27 publications

Smart functional nucleic acid chimeras: Enabling tissue specific RNA targeting therapy

Smart functional nucleic acid chimeras: Enabling tissue specific RNA targeting therapy

Stabilizing contributions of sulfur-modified nucleotides: crystal structure of a DNA duplex with 2'-O-[2-(methoxy)ethyl]-2-thiothymidines

Synthesis of the DNA−[Ru(tpy)(dppz)(CH₃CN)]²⁺ Conjugates and Their Photo Cross-Linking Studies with the Complementary DNA Strand

Contact Info

Product

Resources

About

Antisense Oligonucleotides

Cited by 425 publications

References 27 publications

Smart functional nucleic acid chimeras: Enabling tissue specific RNA targeting therapy

Smart functional nucleic acid chimeras: Enabling tissue specific RNA targeting therapy

Stabilizing contributions of sulfur-modified nucleotides: crystal structure of a DNA duplex with 2'-O-[2-(methoxy)ethyl]-2-thiothymidines

Synthesis of the DNA−[Ru(tpy)(dppz)(CH3CN)]2+ Conjugates and Their Photo Cross-Linking Studies with the Complementary DNA Strand

Contact Info

Product

Resources

About

Synthesis of the DNA−[Ru(tpy)(dppz)(CH₃CN)]²⁺ Conjugates and Their Photo Cross-Linking Studies with the Complementary DNA Strand