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Search for "nucleobase modifications" in Full Text gives 4 result(s) in Beilstein Journal of Organic Chemistry.
Cationic oligonucleotide derivatives and conjugates: A favorable approach for enhanced DNA and RNA targeting oligonucleotides
- Mathias B. Danielsen and
- Jesper Wengel
Beilstein J. Org. Chem. 2021, 17, 1828–1848, doi:10.3762/bjoc.17.125
- , and examining the future design for ASOs. Keywords: antisense oligonucleotides; backbone modifications; cations; nucleobase modifications; sugar modifications; Introduction Antisense oligonucleotides (ASOs) are single-stranded (ss) oligomers composed of typically 10–25 nucleotides linked by
- the cationic moiety emerges. Additionally, sugar modifications tend to bring higher nuclease resistance compared with nucleobase modifications. However, a drawback is the lack of RNase H activation for most of the sugar-modified derivatives. This is contrary to the nucleobase-modified variants that
Graphical Abstract
Figure 1: A schematic representation of 16-mer ASOs in different designs. White circles represent unmodified ...
Figure 2: Structures of 5-(1-propargylamino)-2’-deoxyuridine (A) and 2’-aminoethoxy-5-propargylaminouridine (...
Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications
- Nikita Brodyagin,
- Martins Katkevics,
- Venubabu Kotikam,
- Christopher A. Ryan and
- Eriks Rozners
Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116
- noted that PNA forms duplexes with complementary DNA and RNA that are more stable than duplexes involving only natural nucleic acids. Nevertheless, nucleobase modifications can further improve the remarkable binding properties of PNAs. One of the most promising nucleobases for improving Watson–Crick
Graphical Abstract
Figure 1: Structure of DNA and PNA.
Figure 2: PNA binding modes: (A) PNA–dsDNA 1:1 triplex; (B) PNA–DNA–PNA strand-invasion triplex; (C) the Hoog...
Figure 3: Structure of P-form PNA–DNA–PNA triplex from reference [41]. (A) view in the major groove and (B) view ...
Figure 4: Structures of backbone-modified PNA.
Figure 5: Structures of PNA having α- and γ-substituted backbones.
Figure 6: Structures of modified nucleobases in PNA to improve Hoogsteen hydrogen bonding to guanine and aden...
Figure 7: Proposed hydrogen bonding schemes for modified PNA nucleobases designed to recognize pyrimidines or...
Figure 8: Modified nucleobases to modulate Watson–Crick base pairing and chemically reactive crosslinking PNA...
Figure 9: Examples of triplets formed by Janus-wedge PNA nucleobases (blue). R1 denotes DNA, RNA, or PNA back...
Figure 10: Examples of fluorescent PNA nucleobases. R1 denotes DNA, RNA, or PNA backbones.
Figure 11: Endosomal entrapment and escape pathways of PNA and PNA conjugates.
Figure 12: (A) representative cell-penetrating peptides (CPPs), (B) conjugation designs and linker chemistries....
Figure 13: Proposed delivery mode by pHLIP-PNA conjugates (A) the transmembrane section of pHLIP interacting w...
Figure 14: Structures of modified penetratin CPP conjugates with PNA linked through either disulfide (for stud...
Figure 15: Chemical structure of C9–PNA, a stable amphipathic (cyclic-peptide)–PNA conjugate.
Figure 16: Structures of PNA conjugates with a lipophilic triphenylphosphonium cation (TPP–PNA) through (A) th...
Figure 17: Structures of (A) chloesteryl–PNA, (B) cholate–PNA and (C) cholate–PNA(cholate)3.
Figure 18: Structures of PNA–GalNAc conjugates (A) (GalNAc)2K, (B) triantennary (GalNAc)3, and (C) trivalent (...
Figure 19: Vitamin B12–PNA conjugates with different linkages.
Figure 20: Structures of (A) neomycin B, (B) PNA–neamine conjugate, and (C) PNA–neosamine conjugate.
Figure 21: PNA clamp (red) binding to target DNA containing a mixture of sequences (A) PNA binds with higher a...
Figure 22: Rolling circle amplification using PNA openers (red) to invade a dsDNA target forming a P-loop. A p...
Figure 23: Molecular beacons containing generic fluorophores (Fl) and quenchers (Q) recognizing a complementar...
Figure 24: (A) Light-up fluorophores such as thiazole orange display fluorescence enhancement upon binding to ...
Figure 25: Templated fluorogenic detection of oligonucleotides using two PNAs. (A) Templated FRET depends on h...
Figure 26: Lateral flow devices use a streptavidin labeled strip on nitrocellulose paper to anchor a capture P...
Beyond ribose and phosphate: Selected nucleic acid modifications for structure–function investigations and therapeutic applications
- Christopher Liczner,
- Kieran Duke,
- Gabrielle Juneau,
- Martin Egli and
- Christopher J. Wilds
Beilstein J. Org. Chem. 2021, 17, 908–931, doi:10.3762/bjoc.17.76
- target effects [54]. Sugar and nucleobase modifications 2'-O-Alkyl modifications Historically, the 2'-OMe modification (Figure 5A) was the first of its class. The synthesis of each 2'-OMe ribonucleoside required specific considerations [108]. Starting from 3',5'-O-(tetraisopropyldisiloxane-1,3-diyl
Graphical Abstract
Figure 1: Structures of the chemically modified oligonucleotides (A) N3' → P5' phosphoramidate linkage, (B) a...
Scheme 1: Synthesis of a N3' → P5' phosphoramidate linkage by solid-phase synthesis. (a) dichloroacetic acid;...
Figure 2: Crystal structures of (A) N3' → P5' phosphoramidate DNA (PDB ID 363D) [71] and (B) amide (AM1) RNA in c...
Scheme 2: Synthesis of a phosphorodithioate linkage by solid-phase synthesis. (a) detritylation; (b) tetrazol...
Figure 3: Close-up view of a key interaction between the PS2-modified antithrombin RNA aptamer and thrombin i...
Scheme 3: Synthesis of the (S)-GNA thymine phosphoramidite from (S)-glycidyl 4,4'-dimethoxytrityl ether. (a) ...
Figure 4: Surface models of the crystal structures of RNA dodecamers with single (A) (S)-GNA-T (PDB ID 5V1L) [54]...
Figure 5: Structures of 2'-O-alkyl modifications. (A) 2'-O-methoxy RNA (2'-OMe RNA), (B) 2'-O-(2-methoxyethyl...
Scheme 4: Synthesis of the 2'-OMe uridine from 3',5'-O-(tetraisopropyldisiloxane-1,3-diyl)uridine. (a) Benzoy...
Scheme 5: Synthesis of the 2'-O-MOE uridine from uridine. (a) (PhO)2CO, NaHCO3, DMA, 100 °C; (b) Al(OCH2CH2OCH...
Figure 6: Structure of 2'-O-(2-methoxyethyl)-RNA (MOE-RNA). (A) View into the minor groove of an A-form DNA d...
Figure 7: Structures of locked nucleic acids (LNA)/bridged nucleic acids (BNA) modifications. (A) LNA/BNA, (B...
Scheme 6: Synthesis of the uridine LNA phosphoramidite. (a) i) NaH, BnBr, DMF, ii) acetic anhydride, pyridine...
Scheme 7: Synthesis of the 2'-fluoroarabinothymidine. (a) 30% HBr in acetic acid; (b) 2,4-bis-O-(trimethylsil...
Figure 8: Sugar puckers of arabinose (ANA) and arabinofluoro (FANA) nucleic acids compared with the puckers o...
Figure 9: Structures of C4'-modified nucleic acids. (A) 4'-methoxy, (B) 4'-(2-methoxyethoxy), (C) 2',4'-diflu...
Scheme 8: Synthesis of the 4'-F-rU phosphoramidite. (a) AgF, I2, dichloromethane, tetrahydrofuran; (b) NH3, m...
Scheme 9: Synthesis of the thymine FHNA phosphoramidite. (a) thymine, 1,8-diazabicyclo[5.4.0]undec-7-ene, ace...
Scheme 10: Synthesis of the thymine Ara-FHNA phosphoramidite. (a) i) trifluoromethanesulfonic anhydride, pyrid...
Figure 10: Crystal structures of (A) FHNA and (B) Ara-FHNA in modified A-form DNA decamers (PDB IDs 3Q61 and 3...
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
- thymine-modified ONs and their complementary sequences were evaluated; the nucleobase modifications induced an important destabilization of the duplexes. This result suggests that 4-NO2-benzylthymine-modified ONs cannot hybridize to their targets and consequently should be inactive in normal cells
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-...
