Nucleoside Phosphoramidites Containing Cleavable Linkers

Pon, Richard T.

doi:10.1002/0471142700.nc0312s23

Cited by 3 publications

(3 citation statements)

References 33 publications

(46 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Derivatization of oligonucleotides by covalent attachment of a non-oligonucleotide moiety, usually referred to as conjugation, is a common alternative to improve oligonucleotides performance in biological assays and suitability for therapeutic applications 15 (1). 3'-Modification is known to impart protection to the most ubiquitous nucleases, namely 3'-exonucleases (2), and conjugation often improves oligonucleotides' cell permeation properties.…”

Section: Introductionmentioning

confidence: 99%

“…Even though this type of reactions takes place on a solid matrix, which allows large excesses of the activated 5 carboxyl-containing species to be added, coupling yields have been described as poorly reproducible and not always fully satisfactory (13). Incorporation of a protected maleimido unit after oligonucleotide elongation using standard nucleoside-3'-phosphoramidite derivatives, followed by deprotection with ammonia and heating to provide the free maleimide (retro-Diels-Alder reaction), 15 affords 5'-maleimido-oligonucleotides. Chain elongation with nucleoside-5'-phosphoramidites might allow 3'-maleimidooligonucleotides to be assembled, but these derivatives are much more expensive than standard nucleoside-3'-phosphoramidite.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Easy introduction of maleimides at different positions of oligonucleotide chains for conjugation purposes

2012

View full text Add to dashboard Cite

5[2,5-dimethylfuran]-protected maleimides were placed at both internal positions and the 3'-end of oligonucleotides making use of solid-phase synthesis procedures. A new phosphoramidite derivative and a new solid support incorporating the protected maleimide moiety were prepared for this purpose. In all cases maleimide deprotection (retro-Diels-Alder reaction) followed by reaction with thiol-containing compounds afforded the target conjugate.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Easy introduction of maleimides at different positions of oligonucleotide chains for conjugation purposes

2012

View full text Add to dashboard Cite

show abstract

“…Recently, a solution-phase approach has been evaluated as a scalable route for the large-scale synthesis of therapeutic oligonucleotides. 5 The growing demand for synthetic DNA and RNA and its analogues as therapeutics 6 and reagents for diagnostic 7 applications has triggered a need for improved synthetic protocols 5,8 and the development of new protecting reagents. 9 Despite the mentioned advantages, application of compound 1 in nucleic acid chemistry is limited by its susceptibility to base treatment.…”

mentioning

confidence: 99%

1,2-Ethylene-3,3-bis(4′,4′′-dimethoxytrityl Chloride) (E-DMT): Synthesis and Applications of a Novel Protecting Reagent

Oka¹,

Sanghvi²,

Theodorakis³

2004

Synlett

View full text Add to dashboard Cite

1,2-Ethylene-3,3-bis(4¢,4¢¢-dimethoxytrityl chloride), (E-DMT) was developed as a novel, bifunctional protecting reagent. This new compound was found to have a potential as a multipurpose acid-labile protecting reagent which can afford a 5¢,5¢-tritylthymidine dimer and a unique 5¢,3¢-cyclic protected thymidine derivative in modest to good yields.Triphenylmethyl (trityl) group and its derivatives have been widely used for the protection of hydroxyl, amino, and carboxyl groups. The usefulness and importance of the trityl group are clearly demonstrated by (i) highly selective protection of less-hindered functional groups, (ii) stability under neutral or alkaline conditions, (iii) cleavage under mild acidic conditions, (iv) remarkable hydrophobicity, and (v) sensitive detection of the corresponding trityl cation by visual or spectrophotometric methods. 1 Due to these advantages, the trityl groups and in particular its 4¢,4¢¢-dimethoxy trityl (DMT) analogue are widely used for the protection of the 5¢-hydroxyl group during DNA and RNA synthesis. 2In addition to these conventional monofunctional trityl groups, some bis(trityl chloride)s having two trityl chlorides connected with a bifunctional ester linkage have been reported by Köster et al. as a scaffold for solutionphase DNA synthesis (1, Figure 1). 3 These bifunctional trityl chlorides 4 can react with 2 equivalents of a thymidine derivative at the 5¢-OH group allowing synthesis of two strands of DNA via the 3¢-ends. This method significantly differentiates the trityl bearing two oligonucleotide chains from the monomers in molecular size to enable a facile purification of the trityl bearing oligonucleotide by size exclusion gel permeation chromatography. Recently, a solution-phase approach has been evaluated as a scalable route for the large-scale synthesis of therapeutic oligonucleotides. 5 The growing demand for synthetic DNA and RNA and its analogues as therapeutics 6 and reagents for diagnostic 7 applications has triggered a need for improved synthetic protocols 5,8 and the development of new protecting reagents. 9Despite the mentioned advantages, application of compound 1 in nucleic acid chemistry is limited by its susceptibility to base treatment. This limitation is particularly significant for large-scale solution-phase synthesis of oligonucleotides where extensive treatment with ammonium hydroxide is required. We envisioned that this issue could be addressed if the two-trityl groups could be linked together via an all carbon bridge. This modification would lead to a chemically stable bis(trityl) group amenable for oligonucleotide synthesis. Moreover such a protecting group could be recovered and recycled to make the process environmentally friendly. 10 Our continued interest in the development of novel protecting groups 11 prompted us to explore the synthesis of 1,2-ethylene-3,3-bis(4¢,4¢¢-dimethoxytrityl chloride) (E-DMT, 2; Figure 1). Herein, we wish to report our results on the expeditious synthesis of E-DMT and show the preliminary results of potential ...

show abstract

Green synthesis of phosphoramidates and evaluation of their α-amylase activity by in silico and in vitro studies

Shaik

Nadiveedhi

Gundluru

et al. 2021

Synthetic Communications

View full text Add to dashboard Cite

Nucleoside Phosphoramidites Containing Cleavable Linkers

Cited by 3 publications

References 33 publications

Easy introduction of maleimides at different positions of oligonucleotide chains for conjugation purposes

Easy introduction of maleimides at different positions of oligonucleotide chains for conjugation purposes

1,2-Ethylene-3,3-bis(4′,4′′-dimethoxytrityl Chloride) (E-DMT): Synthesis and Applications of a Novel Protecting Reagent

Green synthesis of phosphoramidates and evaluation of their α-amylase activity by in silico and in vitro studies

Contact Info

Product

Resources

About