Cationic oligonucleotide derivatives and conjugates: A favorable approach for enhanced DNA and RNA targeting oligonucleotides
| Autor: | Jesper Wengel, Mathias B. Danielsen |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Science Organic chemistry nucleobase modifications Review Cations 01 natural sciences Nucleobase 03 medical and health sciences chemistry.chemical_compound QD241-441 Backbone modifications Nuclease Antisense oligonucleotides biology backbone modifications 010405 organic chemistry Oligonucleotide Cationic polymerization Combinatorial chemistry cations sugar modifications 0104 chemical sciences Chemistry 030104 developmental biology chemistry Nucleic acid biology.protein Amine gas treating Sugar modifications antisense oligonucleotides DNA Conjugate |
| Zdroj: | Beilstein Journal of Organic Chemistry, Vol 17, Iss 1, Pp 1828-1848 (2021) Danielsen, M B & Wengel, J 2021, ' Cationic oligonucleotide derivatives and conjugates : A favorable approach for enhanced DNA and RNA targeting oligonucleotides ', Beilstein Journal of Organic Chemistry, vol. 17, pp. 1828-1848 . https://doi.org/10.3762/bjoc.17.125 Beilstein Journal of Organic Chemistry |
| ISSN: | 1860-5397 |
| Popis: | Antisense oligonucleotides (ASOs) have the ability of binding to endogenous nucleic acid targets, thereby inhibiting the gene expression. Although ASOs have great potential in the treatment of many diseases, the search for favorable toxicity profiles and distribution has been challenging and consequently impeded the widespread use of ASOs as conventional medicine. One strategy that has been employed to optimize the delivery profile of ASOs, is the functionalization of ASOs with cationic amine groups, either by direct conjugation onto the sugar, nucleobase or internucleotide linkage. The introduction of these positively charged groups has improved properties like nuclease resistance, increased binding to the nucleic acid target and improved cell uptake for oligonucleotides (ONs) and ASOs. The modifications highlighted in this review are some of the most prevalent cationic amine groups which have been attached as single modifications onto ONs/ASOs. The review has been separated into three sections, nucleobase, sugar and backbone modifications, highlighting what impact the cationic amine groups have on the ONs/ASOs physiochemical and biological properties. Finally, a concluding section has been added, summarizing the important knowledge from the three chapters, and examining the future design for ASOs. |
| Databáze: | OpenAIRE |
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