Solid-phase stereoselective synthesis of 2′-O-methyl-oligoribonucleoside phosphorothioates using nucleoside bicyclic oxazaphospholidines

Guo, Mao‐Jun; Yu, Dong; Iyer, Radhakrishnan P.; Agrawal, Sudhir

doi:10.1016/s0960-894x(98)00450-8

Cited by 28 publications

(18 citation statements)

References 9 publications

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“…89 Since then, many methods for the stereocontrolled synthesis of PS-ODN have been developed. [90][91][92][93][94][95][96][97][98] In 1995 the group of Stec described the difference in activity of RNase-H during the hydrolysis of a hybridized 15-mer oligoribonucleotide (ORN) to its complementary PO, mix-PS, all-R p -PS or all-S p -PS-ODN. 86 The experiments were conducted with either 1 or 3 equivalents of the ODN compared to the ORN at 28 or 37 1C for 45 min before analysis ( Table 5).…”

Section: Ps C Ps a Ps C Ps A Ps C Ps C-gacg Ps G Ps C Ps G Ps C Ps mentioning

confidence: 99%

Modified internucleoside linkages for nuclease-resistant oligonucleotides

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Section: Ps C Ps a Ps C Ps A Ps C Ps C-gacg Ps G Ps C Ps G Ps C Ps mentioning

confidence: 99%

Modified internucleoside linkages for nuclease-resistant oligonucleotides

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“…Testing of this only awaited the solid-phase synthesis of stereo-enriched and stereo-pure PS-ODNs. This became possible through pioneering work of Stec and later by use of nucleoside bicyclic oxazaphospholidinium synthons [ 15 , 60 ]. It is now known that binding strength and recognition by RNase H is generally higher for antisense oligonucleotides containing R p linkages but depends crucially on the placement of these with respect to S p linkages and overall stereospecific PS-ODNs have had limited therapeutic utility [ 61 ].…”

Section: Synthetic Oligonucleotide Analogues In Antisense and Sirnamentioning

confidence: 99%

Introduction and History of the Chemistry of Nucleic Acids Therapeutics

Gait

Agrawal

2022

Methods in Molecular Biology

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This introduction charts the history of the development of the major chemical modifications that have influenced the development of nucleic acids therapeutics focusing in particular on antisense oligonucleotide analogues carrying modifications in the backbone and sugar. Brief mention is made of siRNA development and other applications that have by and large utilized the same modifications. We also point out the pitfalls of the use of nucleic acids as drugs, such as their unwanted interactions with pattern recognition receptors, which can be mitigated by chemical modification or used as immunotherapeutic agents.

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“… 43 , 44 In a shift that mirrored phosphodiester synthesis, the field moved to P(III) to address this issue. Using chiral P(III) derivatives such as the N-acyl oxazaphospholidines, 45 oxazaphosphorinanes, 46 − 49 and oxazaphospholidines 50 , 51 remedied the poor coupling efficiency problem, but suffered from a lack of stereoselectivity, either in synthesis of the monomer units or during SPOS ( Figure 3 A). A decade after their introduction, Wada and co-workers found that bicyclic oxazaphospholidine monomers could be stereospecifically coupled during SPOS when using a novel non-nucleophilic activator.…”

Section: Resurrecting P(v) For Oligonucleotide Synthesismentioning

confidence: 99%

Nature Chose Phosphates and Chemists Should Too: How Emerging P(V) Methods Can Augment Existing Strategies

et al. 2021

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Phosphate linkages govern life as we know it. Their unique properties provide the foundation for many natural systems from cell biology and biosynthesis to the backbone of nucleic acids. Phosphates are ideal natural moieties; existing as ionized species in a stable P(V)-oxidation state, they are endowed with high stability but exhibit enzymatically unlockable potential. Despite intense interest in phosphorus catalysis and condensation chemistry, organic chemistry has not fully embraced the potential of P(V) reagents. To be sure, within the world of chemical oligonucleotide synthesis, modern approaches utilize P(III) reagent systems to create phosphate linkages and their analogs. In this Outlook, we present recent studies from our laboratories suggesting that numerous exciting opportunities for P(V) chemistry exist at the nexus of organic synthesis and biochemistry. Applications to the synthesis of stereopure antisense oligonucleotides, cyclic dinucleotides, methylphosphonates, and phosphines are reviewed as well as chemoselective modification to peptides, proteins, and nucleic acids. Finally, an outlook into what may be possible in the future with P(V) chemistry is previewed, suggesting these examples represent just the tip of the iceberg.

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Solid-phase stereoselective synthesis of 2′-O-methyl-oligoribonucleoside phosphorothioates using nucleoside bicyclic oxazaphospholidines

Cited by 28 publications

References 9 publications

Modified internucleoside linkages for nuclease-resistant oligonucleotides

Modified internucleoside linkages for nuclease-resistant oligonucleotides

Introduction and History of the Chemistry of Nucleic Acids Therapeutics

Nature Chose Phosphates and Chemists Should Too: How Emerging P(V) Methods Can Augment Existing Strategies

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