Synthesis of Novel Representatives of Phosphoryl Guanidine Oligonucleotides

Zhukov, S. A.; Пышный, Д. В.; Kupryushkin, Maxim S.

doi:10.1134/s1068162021020291

Cited by 9 publications

(16 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It should be noted that the modification with azide 4 after deprotection results in an uncharged phosphate group ( Scheme 4 ) similar to the dimethylimidazole one. 13 …”

Section: Resultsmentioning

confidence: 99%

“…Modified oligonucleotides have reduced charge than unmodified T6. Dimethylbenzimidazole (DMBI) modifying group results in uncharged nucleotide similar to the dimethylimidazole one 13 while being the closest in the mass and structure to N -benz-imida(oxa/thia)zole groups. The N -benzimidazole group (line 2) appears to be protonated under all studied pH ( Figure 2 A–C).…”

Section: Resultsmentioning

confidence: 99%

“…An interesting and rapidly developing method for obtaining new modifications of the inter-nucleotide bond is the one with the use of the Staudinger reaction . This reaction between the esters of 3′,5′-dinucleoside phosphites and organic azides has been used previously to introduce N -sulfonylphosphoramide groups − and N -alkylphosphoramide groups , into the oligonucleotide. The phosphoryl guanidine and mesyl phosphoramidate oligonucleotides are particularly important as potential splice-switching agents …”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Synthesis of Oligonucleotides Carrying Inter-nucleotide N-(Benzoazole)-phosphoramide Moieties

et al. 2022

View full text Add to dashboard Cite

In this work, we present new oligonucleotide derivatives containing inter-nucleotide N-benzimidazole, N-benzoxazole, N-benzothiazole, and 1,3-dimethyl-N-benzimidazole (benzoazoles) phosphoramide groups. These modifications were introduced via the Staudinger reaction with appropriate azides during standard automated solid-phase oligonucleotide synthesis. The principal structural difference between the new azido modifiers and those already known is that they are bulk heterocyclic structures, similar to purine nucleoside bases. Modified oligonucleotides with one and two modifications at different positions and multiple modified heteronucleotide sequences were obtained with high yields. The possibility of multiple modifications in the process of automatic DNA synthesis is fundamental and critical for further application of our oligonucleotide derivatives. Initial studies on the properties of new oligonucleotides were carried out. The stability of the oligodeoxyribonucleotide duplex containing phosphoramide groups of N-benzoazoles with complementary DNA or RNA is slightly lower than that of native complexes.

show abstract

“…It should be noted that the modification with azide 4 after deprotection results in an uncharged phosphate group ( Scheme 4 ) similar to the dimethylimidazole one. 13 …”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Synthesis of Oligonucleotides Carrying Inter-nucleotide N-(Benzoazole)-phosphoramide Moieties

et al. 2022

View full text Add to dashboard Cite

show abstract

“…1i) [71,72] . The PN and MsPA groups represent relatively new chemistries that are highly resistant to nucleases and are easily incorporated into the solid-phase synthesis cycle by substituting an azide synthon for sulfur during P(II) to P(V) conversion [73] .…”

Section: Phosphorothioate Linkages -The Dr Jekyll and Mr Hyde Of Olig...mentioning

confidence: 99%

Future directions for medicinal chemistry in the field of oligonucleotide therapeutics

Hall

2023

RNA

View full text Add to dashboard Cite

show abstract

“…Over the past decade, several chemical approaches utilizing alternative oxidation steps to obtain novel structures of modified phosphate groups, which allow one not only to change the nature of the phosphate backbone but also to apply the chemistry of its introduction to varying desirable functional moieties, have been proposed [ 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ]. In particular, we have adopted the method of using electron-deficient azides in the Staudinger reaction during the oxidation step to efficiently obtain various phosphate derivatives [ 34 , 35 , 36 , 37 , 38 , 39 ]. We have also demonstrated that different representatives of the developed phosphoryl guanidine and triazinyl phosphoramidate modifications can be applied for the synthesis of lipophilic oligonucleotides with enhanced levels of intracellular accumulation [ 37 ].…”

Section: Introductionmentioning

confidence: 99%

Influence of Combinations of Lipophilic and Phosphate Backbone Modifications on Cellular Uptake of Modified Oligonucleotides

Zharkov,

Markov,

Zhukov

et al. 2024

Molecules

View full text Add to dashboard Cite

Numerous types of oligonucleotide modifications have been developed since automated synthesis of DNA/RNA became a common instrument in the creation of synthetic oligonucleotides. Despite the growing number of types of oligonucleotide modifications under development, only a few of them and, moreover, their combinations have been studied widely enough in terms of their influence on the properties of corresponding NA constructions. In the present study, a number of oligonucleotides with combinations of 3′-end lipophilic (a single cholesteryl or a pair of dodecyl residues) and phosphate backbone modifications were synthesized. The influence of the combination of used lipophilic groups with phosphate modifications of various natures and different positions on the efficiency of cell penetration was evaluated. The obtained results indicate that even a couple of phosphate modifications are able to affect a set of oligonucleotide properties in a complex manner and can remarkably change cellular uptake. These data clearly show that the strategy of using different patterns of modification combinations has great potential for the rational design of oligonucleotide structures with desired predefined properties.

show abstract

Synthesis of Novel Representatives of Phosphoryl Guanidine Oligonucleotides

Cited by 9 publications

References 12 publications

Synthesis of Oligonucleotides Carrying Inter-nucleotide N-(Benzoazole)-phosphoramide Moieties

Synthesis of Oligonucleotides Carrying Inter-nucleotide N-(Benzoazole)-phosphoramide Moieties

Future directions for medicinal chemistry in the field of oligonucleotide therapeutics

Influence of Combinations of Lipophilic and Phosphate Backbone Modifications on Cellular Uptake of Modified Oligonucleotides

Contact Info

Product

Resources

About