Enhancement of the affinity of 2′-O-Me-oligonucleotides for complementary RNA by incorporating a stereoregulated boranophosphate backbone

Nukaga, Yohei; Takemura, Tetsuhiko; Iwamoto, Naoki; Oka, Natsuhisa; Wada, Takehiko

doi:10.1039/c4ra11335g

Cited by 10 publications

(3 citation statements)

References 30 publications

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“…Notably, ( S p)-PB/PO chimeric U 12 formed a marked stable duplex. This result agrees well with our previous report that an all-( S p)-PB 2′- O -Me decauridylate formed a more stable duplex with a complementary ORN than an unmodified counterpart, whereas the T m value of an all-( R p)-PB 2′- O -Me decauridylate and complementary ORN could not be determined owing to the instability of duplex [34]. From the observation of melting curves, it was suggested that the duplex of ( R p)-PB/PO chimeric U 12 and A 12 had a small hyperchromicity compared to the other duplexes.…”

Section: Resultssupporting

confidence: 92%

Solid-phase synthesis and properties of stereocontrolled boranophosphate/phosphate and phosphorothioate/phosphate chimeric oligouridylates

2023

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This study describes the stereoselective synthesis of boranophosphate/phosphate (PB/PO) and phosphorothioate/phosphate (PS/PO) chimeric oligouridylates using the solid-phase method. Oxazaphospholidine monomer was used to construct the stereodefined PB and PS linkages. The study introduces modifications to oligouridylate derivatives in the intended positions with the intended stereochemistry of phosphorous atoms. Additionally, biophysical and biochemical properties of the synthesized oligomers were evaluated. Notably, it was found that a ( S p)-PB/PO chimeric oligouridylate had higher hybridization ability than the unmodified counterpart to an unmodified oligoadenylate. This is the first report that elucidates the effect of both stereochemistry and type of P -modification (PB and PS) on properties of oligoribonucleotides.

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Section: Resultssupporting

confidence: 92%

Solid-phase synthesis and properties of stereocontrolled boranophosphate/phosphate and phosphorothioate/phosphate chimeric oligouridylates

2023

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“… , In this approach, the boronating reaction can be conducted after all of the base-protecting groups are removed, different from the conventional phosphoramidite method. Unprotected nucleobases were previously demonstrated not to cause any side reactions in the coupling reaction. − The strategy worked to some extent and homo-T and 2′-OMe-modified homo-rU 12mers, and PB-dCAGT (4mer) could be synthesized in a stereocontrolled manner. ,, However, the coupling efficiency was not enough to synthesize nucleic acid oligomers with all four nucleobases longer than 4mer by this strategy. One probable reason for the low coupling efficiency is that the steric hindrance of both protecting groups on nucleobases and substituents on the oxazaphospholidine ring is larger than that of the conventional oxazaphospholidine approach.…”

Section: Introductionmentioning

confidence: 99%

Stereocontrolled Synthesis of Boranophosphate DNA by an Oxazaphospholidine Approach and Evaluation of Its Properties

et al. 2019

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In this paper, we describe the first stereocontrolled synthesis and properties of boranophosphate DNA (PB-DNA), which contains all of the four nucleobases longer than 10mer. Synthesis was accomplished via an oxazaphospholidine approach combined with acid-labile protecting groups on nucleobases. It was demonstrated that there were significant differences between all-(Rp)-and all-(Sp)-PB-DNA in terms of the duplex-formation ability, nuclease resistance, and ribonuclease H (RNase H) activity. In particular, all-(Sp)-PB-DNA was demonstrated to show a duplexformation ability with RNA and RNase H activity, both of which are necessary for antisense-type nucleic acid therapeutics.

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“…We have previously developed a method for synthesizing stereocontrolled P -chiral oligonucleotides using nucleoside 3′- O -oxazaphospholidine derivatives as monomers (the oxazaphospholidine method) . The oxazaphospholidine monomers can be stereoselectively synthesized from enantiopure 1,2-amino alcohols as chiral auxiliaries with d.r.…”

Section: Introductionmentioning

confidence: 99%

Stereocontrolled Solid-Phase Synthesis of Phosphate/Phosphorothioate (PO/PS) Chimeric Oligodeoxyribonucleotides on an Automated Synthesizer Using an Oxazaphospholidine–Phosphoramidite Method

2016

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Stereocontrolled solid-phase synthesis of phosphate/phosphorothioate chimeric oligodeoxyribonucleotides (PO/PS-ODNs) was achieved by integrating the conventional phosphoramidite method into a previously developed oxazaphospholidine method for the stereocontrolled synthesis of P-chiral oligonucleotides. P-Stereodefined PO/PS-ODNs with mixed sequences (up to 12-mers) were obtained in good yields and high stereoselectivities by reacting different combinations of monomers (conventional phosphoramidites/diastereopure nucleoside 3'-O-oxazaphospholidines), activators (ETT/CMPT), capping reagents (Pac2O/CF3COIm), and oxidizing/sulfurizing reagents (TBHP/POS) on an automated synthesizer. A thermal denaturation study examined the resultant diastereopure PO/PS-ODN 12-mers with three consecutive (Rp)- or (Sp)-PS-linkages at the internal or terminal regions of the molecules. We found that (Rp)-PO/PS-ODNs can only moderately destabilize duplexes with complementary oligoribonucleotides (ORNs) compared with their unmodified ODN counterparts (ΔTm = -0.4 °C per modification). In contrast, (Sp)-PO/PS-ODNs have larger destabilizing effects (ΔTm = -1.2 to -0.8 °C per modification). Although smaller destabilizing effects were observed when the (Sp)-PS-linkages were incorporated into the terminal regions of the molecule, there was a weaker correlation between the location of an incorporated (Rp)-PS-linkage and its destabilizing effect.

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Enhancement of the affinity of 2′-O-Me-oligonucleotides for complementary RNA by incorporating a stereoregulated boranophosphate backbone

Abstract: P-stereodefined boranophosphate 2′-O-Me-oligoribonucleotides (2′-O-Me-PB-ORNs) were synthesized and we revealed that an all-(Sp)-PB-backbone largely stabilized the duplex with RNA.

Cited by 10 publications

References 30 publications

Solid-phase synthesis and properties of stereocontrolled boranophosphate/phosphate and phosphorothioate/phosphate chimeric oligouridylates

Solid-phase synthesis and properties of stereocontrolled boranophosphate/phosphate and phosphorothioate/phosphate chimeric oligouridylates

Stereocontrolled Synthesis of Boranophosphate DNA by an Oxazaphospholidine Approach and Evaluation of Its Properties

Stereocontrolled Solid-Phase Synthesis of Phosphate/Phosphorothioate (PO/PS) Chimeric Oligodeoxyribonucleotides on an Automated Synthesizer Using an Oxazaphospholidine–Phosphoramidite Method

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