Synthesis and Hybridization Properties of an Oligonucleotide Consisting of 1′,4′-Anhydro-2′,5′-dideoxy-2′-(thymin-1-yl)-D-altritol

Zhu, Ge; Tian, Xiaobin; Zhang, Liangren; Min, Ji-Mei; Zhang, Lihe

doi:10.1002/1522-2675(200205)85:5<1479::aid-hlca1479>3.0.co;2-p

Cited by 9 publications

(5 citation statements)

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“…In our previous reports for synthesis and incorporation of isonucleosides into antisense oligos, we found that modified antisense oligos not only possess strong nuclease resistance but more interestingly become good substrates of RNase H (20). CD spectra and molecular modeling demonstrated that isonucleoside-modified DNA duplexes still adopt a B-like conformation, but the formation of Watson-Crick hydrogen bonding was perturbed by the torsion of the backbone (21,22), while isonucleosidemodified oligonucleotide/RNA duplex formed an A-like conformation in solution (23). An introduction of an amino group into the isonucleoside may increase the thermal stability of the isonucleoside-modified oligonucleotide with its complementary sequence.…”

Section: Introductionmentioning

confidence: 92%

Studies on Aminoisonucleoside Modified siRNAs: Stability and Silencing Activity

Qiao

et al. 2007

Bioconjugate Chem.

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A novel class of aminoisonucleoside was synthesized and incorporated into a luciferase gene-targeting siRNA. Structural and functional analyses of such a kind of siRNAs indicated that sense strand modifications with aminoisonucleoside at the 3' or 5' terminal, such as ssIso-1 and ssIso-2, have less effect on RNA duplex thermal and serum stabilities, and their functional activities are also comparable to their native siRNAs. In contrast, antisense strand modifications with aminoisonucleoside at the corresponding positions, such as asIso-2 or asIso-1, bring a striking negative effect on RNA duplex stability but still maintain around 40-50% of gene knockdown.

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Section: Introductionmentioning

confidence: 92%

Studies on Aminoisonucleoside Modified siRNAs: Stability and Silencing Activity

Qiao

et al. 2007

Bioconjugate Chem.

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“…Besides, the conformational alteration would also have an influence on the hybridization properties of the siRNA duplex, as well as its recognition by other proteins, such as the kinds of nucleases and RNA binding proteins. Isonucleosides (IsoNA) are a novel kind of nucleoside analogue in which the nucleobase is linked to another position of ribose other than C-1′. , In our previous work, we showed that the modified oligonucleotides d -/ l -isoNA 1 and 2 (Figure ) could form a stable duplex with DNA or RNA with a characteristic tertiary conformation as the normal unmodified DNA/RNA duplex. − …”

Section: Introductionmentioning

confidence: 99%

Effects of Conformational Alteration Induced by d-/l-Isonucleoside Incorporation in siRNA on Their Stability in Serum and Silencing Activity

Huang

Chen

et al. 2013

Bioconjugate Chem.

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We report here that all of the d- or l-isonucleoside (isoNA) modified siRNAs investigated showed the characteristic A-form conformation in the circular dichroism (CD) spectra compared to native siRNA. The d-isoNA modification had less influence on the thermal stability of siRNAs, but all l-isoNA modification displayed a significant tendency to decrease the thermal stability of siRNA. It was also found that the stabilities of d-/l-isoNA modified siMek1 in serum were different and d-isoNA modification was more potent, i.e., increase of serum stability of siRNA, than l-isoNA modification. When d-isoNA incorporated at position 4 and position 5 at antisense strand of siMek1 showed obvious improvement on serum stability, however, l-isoNA incorporated at positions 11 and 12 at antisense strand and position 9 at sense strand made the siMek1 duplex formed very unstable in serum. The silencing activities of modified siMek1s with d-/l-isoNA at position 1 of antisense strand also dropped dramatically; however, the modification at 3'-terminal of the sense strand with d- or l-isoNA significantly enhanced the silencing activity targeting the antisense strand as reporter and minimized the passenger strand-specific off-target effect. IsoNA modified in the seed area of siMek1, siMek1 A04D and siMek1 A05L, showed similar activity to the native one and better target selectivity. In the case of modification at the position near the cleavage area, it was found that d- or l-isoNA modified sense strand at position 8, 9, or 15 of siMek1 could retain the silencing activities targeting the antisense strand as reporter. Especially, both siMek1 S15D and siMek1 S15L showed good silencing activity and high target selectivity compared to native siMek1. The effects of conformational alteration of such isoNA modification of siRNA on their stability in serum and silencing activity are discussed based on computer simulation. Systematic investigation of the relationship between modified siRNA conformation and their physical and biological properties should provide a useful guideline for chemical modification and optimization of siRNA for further clinical application.

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“…179 (idT) 13 -dT oligonucleotides containing an extended phosphodiester linkage via the incorporation of 2′,5′-anhydro-3′deoxy-3′-(thymin-1-yl)-D-altritol building blocks (o7) can form stable duplexes with (dA) 14 but with a much reduced T m (28.8 °C vs 35.5 °C for (dT) 14 •(dA) 14 ). 180 With RNA (A 14 ), a more stable duplex (T m of 31.5 °C) can be obtained. CD spectra indicate that duplexes are formed (A-form with RNA).…”

Section: Isonucleic Acids (Inas)mentioning

confidence: 99%

“…166 (idT) 13 -dT oligonucleotides containing D-arabinitol-, L-arabinitol-, or D-altritol-modified T nucleotides (o7) show no degradation by SVPDE after 30 min. 172,180 When D-arabinitol-modified A and T nucleotides (o1) are introduced into the d(GTAGAATTCTAC) sequence, both the SVPDE and the calf spleen phosphodiesterase (a 5′−3′exonuclease) resistances increase with an increasing number of modified nucleotides. 165 The (idAdT) 6 -dT sequence containing the D-arabinitol-modified A nucleotide is very resistant to exonuclease digestion and only shows 20−30% degradation after 100−120 h. The dinucleotides pidApdC and pdCidU containing the D-arabinitol A or U building blocks show an increased stability to exonucleases, with pdCidU totally resistant to phosphodiesterase cleavage.…”

Section: Isonucleic Acids (Inas)mentioning

confidence: 99%

“…(dT) 14 oligonucleotides containing d -arabinitol-, l -arabinitol-, or l -mannitol-modified T nucleotides ( o1 , o2 , and o3 ) have an increased stability toward SVPDE (a 3′–5′-exonuclease) compared to the natural (dT) 14 . (idT) 13 -dT oligonucleotides containing d -arabinitol-, l -arabinitol-, or d -altritol-modified T nucleotides ( o7 ) show no degradation by SVPDE after 30 min. , …”

Section: Oligonucleotides Containing Nucleobase- or 4′-hydroxymethyl-...mentioning

confidence: 99%

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Nucleosides with Transposed Base or 4′-Hydroxymethyl Moieties and Their Corresponding Oligonucleotides

et al. 2015

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This review focuses on 4'-hydroxymethyl- or nucleobase-transposed nucleosides, nucleotides, and nucleoside phosphonates, their stereoisomers, and their close analogues. The biological activities of all known 4'-hydroxymethyl- or nucleobase-transposed nucleosides, nucleotides, and nucleoside phosphonates as potential antiviral or anticancer agents are compiled. The routes that have been taken for the chemical synthesis of such nucleoside derivatives are described, with special attention to the innovative strategies. The enzymatic synthesis, base-pairing properties, structure, and stability of oligonucleotides containing nucleobase- or 4'-hydroxymethyl-transposed nucleotides are discussed. The use of oligonucleotides containing nucleobase- or 4'-hydroxymethyl-transposed nucleotides as small oligonucleotide (e.g., human immunodeficiency virus integrase) inhibitors, in applications such as antisense therapy, silencing RNA (siRNA), or aptamer selections, is detailed.

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Synthesis and Hybridization Properties of an Oligonucleotide Consisting of 1′,4′-Anhydro-2′,5′-dideoxy-2′-(thymin-1-yl)-D-altritol

Cited by 9 publications

References 9 publications

Studies on Aminoisonucleoside Modified siRNAs: Stability and Silencing Activity

Studies on Aminoisonucleoside Modified siRNAs: Stability and Silencing Activity

Effects of Conformational Alteration Induced by d-/l-Isonucleoside Incorporation in siRNA on Their Stability in Serum and Silencing Activity

Nucleosides with Transposed Base or 4′-Hydroxymethyl Moieties and Their Corresponding Oligonucleotides

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