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Search for "oligonucleotide prodrugs" in Full Text gives 1 result(s) in Beilstein Journal of Organic Chemistry.
Stimuli-responsive oligonucleotides in prodrug-based approaches for gene silencing
- Françoise Debart,
- Christelle Dupouy and
- Jean-Jacques Vasseur
Beilstein J. Org. Chem. 2018, 14, 436–469, doi:10.3762/bjoc.14.32
- group; oligonucleotide prodrugs; reduction-responsive; stimuli-responsive nucleic acids; thermolytic prodrugs; Introduction For past decades, oligonucleotide-based therapies have been widely developed using short synthetic oligonucleotides (ONs) and their chemically modified mimics as powerful tools to
- 1958 [12], a prodrug is an agent that undergoes chemical or enzymatic transformations in vivo to yield the active parent drug. The prodrug approach is used to optimize the physicochemical properties of the drug and to improve its pharmacological and toxicological profile. Oligonucleotide prodrugs that
Graphical Abstract
Scheme 1: Demasking under reducing agents of ON prodrugs modified as phosphotriesters with A) benzyl groups [13] ...
Scheme 2: A) Synthesis via phosphoramidite chemistry and B) demasking under the reducing environment of 2’-O-...
Scheme 3: Synthesis via phosphoramidite chemistry of various 2’-O-alkyldithiomethyl (RSSM)-modified RNAs bear...
Scheme 4: A) siRNA conjugates to cholesterol [19] and B) PNA conjugates to a triphenylphosphonium [20] through a disu...
Scheme 5: Synthesis via phosphoramidite chemistry and deprotection mediated by nitroreductase/NADH of hypoxia...
Scheme 6: Synthesis via phosphoramidite chemistry and conversion mediated by nitroreductase/NADH of hypoxia-a...
Scheme 7: Incorporation of O6-(4-nitrobenzyl)-2’-deoxyguanosine into an ON prone to form a G-quadruplex struc...
Scheme 8: Synthesis and mechanism for the demasking of ON prodrugs from A) S-acylthioethyl phosphotriester [29] a...
Figure 1: Oligothymidylates bearing A) 2,2-bis(ethoxycarbonyl)-3-(pivaloyloxy)propyl- and B) 2-cyano-2(2-phen...
Figure 2: Oligothymidylates containing esterase and thermo-labile (4-acetylthio-2,2-dimethyl-3-oxobutyl) phos...
Scheme 9: Phosphoramidites and the corresponding RNA prodrugs protected as A) t-Bu-SATE, B) OH-SATE and C) A-...
Scheme 10: Mechanism of the hydrolysis of 2’-O-acyloxymethyl ONs mediated by carboxyesterases [46]. The hydrolysis...
Scheme 11: Synthesis of partially 2’-O-PivOM-modified RNAs [49] and 2’-O-PiBuOM-modified RNAs [53] using their corresp...
Figure 3: A) 2’-O-amino and guanidino-containing acetal ester phosphoramidites and B) 2’-O-(amino acid) aceta...
Scheme 12: Prodrugs of tricyclo-ONs functionalized with A) ethyl (tcee-T) and B) hexadecyl (tchd-T) ester func...
Scheme 13: Demasking mechanism of fma thiophosphate triesters in CpG ODN upon heat action [58].
Scheme 14: Thermolytic cleavage of the hydroxy-alkylated thiophosphate and phosphato-/thiophosphato-alkylated ...
Scheme 15: Synthesis via phosphoramidite chemistry and thermolytic cleavage of alkylated (diisopropyl, diethyl...
Scheme 16: Synthesis of thermosensitive prodrugs of ODNs containing fma thiophosphate triesters combined to po...
Scheme 17: Caging of deoxycytidine in methylphosphonate ONs by using the thermolabile phenylsulfonylcarbamoyl ...
Figure 4: Biotinylated 1-(5-(aminomethyl)-2-nitrophenyl)ethyl phosphoramidite used to cage the 5’-end of a si...
Scheme 18: Introduction and cleavage of 1-(4,5-dimethoxy-2-nitrophenyl)ethyl (DMNPE) [74] and cyclododecyl-DMNPE (...
Scheme 19: Post-synthetic introduction of a thioether-enol phosphodiester (TEEP) linkage into a DNAzyme by the...
Scheme 20: A) NPP dT and dG phosphoramidites [91,92] and B) NPOM U and G phosphoramidites [83] used to introduce photocag...
Scheme 21: Introduction of the photocaged 3-NPOM nucleobase into phosphorothioate antisense and morpholino ant...
Scheme 22: Control of the activity of an antisense ODN using a photocaged hairpin [82]. Formation of the hairpin s...
Scheme 23: Control of alternative splicing using phosphorothioate (PS) 2’-OMe-photocaged ONs resulting from th...
Scheme 24: A) Light activation of a photocaged DNAzyme incorporating 3-NPOM thymidine in its catalytic site [87]; ...
Scheme 25: Incorporation of 3-(6-nitropiperonyloxymethyl) (NPOM) thymidine and 4-nitropiperonylethyl (NPE) deo...
Scheme 26: Synthesis of a photocaged DNA decoy from a 3-NPOM thymidine phosphoramidite and release of the NPOM...
Scheme 27: Synthesis of a caged DNA decoy hairpin containing a 7-nitroindole nucleotide and release of the mod...
Figure 5: Caged-2’-adenosines used by MacMillan et al [93,94] (X = O) and Piccirilli et al [95] (X = S) to study RNA mec...
Scheme 28: Synthesis of circular ODNs containing a photolabile linker as described by Tang et al. [101,104].
Scheme 29: Control of RNA digestion with RNase H using light activation of a photocaged hairpin [97].
Scheme 30: Photocontrol of RNA degradation using caged circular antisense ODNs containing a photoresponsive li...
Scheme 31: Control of RNA translation using an “RNA bandage” consisting of two short 2’-OMe ONs linked togethe...
Scheme 32: Control of alternative splicing using photocaged ONs resulting from the incorporation of an o-nitro...
Scheme 33: A) Light deactivation of a photocaged DNAzyme incorporating one photocleavable spacer in its cataly...
Scheme 34: Solid-phase synthesis of a caged vit E-siRNA conjugate and its release upon UV irradiation [106].
Scheme 35: Synthesis of a siRNA conjugated to a nanoparticle (NP) via a cyclooctene heterolinker from a siRNA-...
