Synthesis of Nucleobase-Modified RNA Oligonucleotides by Post-Synthetic Approach
Abstract
:1. Introduction
2. Solid-Phase Synthesis of Modified RNA Oligomers via Phosphoramidite Chemistry
3. Post-Synthetic Strategy for Nucleobase RNA Modifications
3.1. Nucleophilic Aromatic Substitution
3.2. Carbon–Carbon Bond-Forming Reaction via Sonogashira and Stille Couplings
3.3. Cycloaddition Reactions
3.4. Derivatization of Amino-Modified Oligoribonucleotides via Formation of Amide Linkage
3.5. Transformation of Ester Groups
3.6. Post-Synthetic Conversions of Sulfur-Containing RNA Oligomers
3.6.1. Post-Synthetic Conversion of 2-Thiouridine-Modified RNA Oligomers
3.6.2. Post-Synthetic Conversion of 4-Thiouridine-Prefunctionalized RNA Oligomers
3.6.3. Post-Synthetic Formation of Disulfide Crosslinks
4. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
Ac | acetyl |
ACE | bis(2-acetoxyethoxy)methyl |
AMA | ammonia-methylamine solution |
AZT | 3′-azidothymidine |
Bz | benzoyl |
BzH | benzhydryloxybis-(trimethylsiloxy)silyl |
cmnm5ges2U | 5-carboxymethylaminomethyl-2-geranylthiouridine |
cmnm5U | 5-carboxymethylaminomethyluridine |
cnm5U | 5-cyanomethyluridine |
CPG | controlled pore glass |
ct6A | cyclic N6-threonylcarbamoyladenosine |
dbf | dibutylaminomethylene |
DBU | 1,8-diazabicyclo [5.4. 0]undec-7-ene |
DCM | dichloromethane |
DIPEA | N,N-diisopropylethylamine |
dmf | dimethylaminomethylene |
DMTr | 4,4′-dimethoxytrityl |
DOD | bis(trimethylsiloxy)cyclododecyloxysilyl |
DTT | dithiothreitol |
EDC·HCl | 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride |
EPR | electron paramagnetic resonance |
ESI-MS | electrospray ionization mass spectrometry |
FMN | flavin mononucleotide |
Fpmp | 1-(2-fluorophenyl)-4-methoxypiperidin-4-yl |
geBr | geranyl bromide |
ges2U | 2-geranylthiouridine |
H2U | 4-pyrimidinone nucleoside |
HEPES | 4-(2-hydroxyethyl)piperazine-1-ethanesulfonic acid |
HOBt | N-hydroxybenzotriazole |
i6A | N6-isopentenyladenosine |
iBu | isobutyryl |
IE HPLC | ion-exchange high performance liquid chromatography |
iEDDA | inverse electron demand Diels-Alder cycloaddition |
inm5U | 5-(isopentenylaminomethyl)uridine |
m5s2U | 5-methyl-2-thiouridine |
m6A | N6-methyladenosine |
MALDI-ToF-MS | matrix-assisted laser desorption/ionization-time of flight mass spectrometry |
mcm5s2U | 5-metoxycarbonylmethyl-2-thiouridine, |
mnm5ges2U | 5-methylaminomethyl-2-geranylthiouridine |
mnm5s2U | 5-methylaminomethyl-2-thiouridine |
mnm5U | 5-methylaminomethyluridine |
ms2C | 2-methylthiocytidine |
ms2ct6A | 2-methylthio cyclic N6-threonylcarbamoyladenosine |
ms2i6A | 2-methylthio-N6-isopentenyladenosine |
ms2m6A | 2-methylthio-N6-methyladenosine |
ms2t6A | 2-methylthio-N6-threonylcarbamoyladenosine |
msms2i6A | 2-methylthiomethylenethio-N6-isopentenyladenosine |
NHS | N-hydroxysuccinimide |
nm5U | 5-aminomethyluridine |
NMP | N-methyl-2-pyrrolidone |
NPE | 2-(2-nitrophenyl)ethyl |
NPP | 2-(2-nitrophenyl)propyl |
OPiv | pivaloyloxyl |
P(furyl)3 | tri-2-furylphosphine |
Pac | phenoxyacetyl |
PAGE | polyacrylamide gel electrophoresis |
Pd2(dba)3 | tris(dibenzylideneacetone)dipalladium(0) |
PELDOR | pulsed electron-electron double resonance |
Pivom5U | 5-pivaloyloxymethyluridine |
R5H2U | 5-substituted 4-pyrimidinone nucleoside |
R5s2U | 5-substituted 2-thiouridine |
R5U | 5-substituted uridine |
Rb | ribose |
RP HPLC | reverse-phase high performance liquid chromatography |
rt | room temperature |
s2U | 2-thiouridine |
s2Um | 2′-O-methyl-2-thiouridine |
s4dU | 4-thio-2′-deoxyuridine |
s4U | 4-thiouridine |
SNAr | nucleophilic aromatic substitution |
t6A | N6-threonylcarbamoyladenosine |
Tac | 4-(tert-butylphenoxy)acetyl |
TBAF | tetrabutylammonium fluoride |
TBDMS | tert-butyldimethylsilyl |
TBTA | tris[(1-benzy-1H-1,2,3-triazol-4-yl)methyl]amine |
TC | 1,1-dioxo-1l6-thiomorpholine-4-carbothioate |
TEA | triethylamine |
TEA×3HF | triethylamine trihydrofluoride |
TEAA | triethylammonium acetate |
TEAF | triethylammonium fluoride |
TEG | triethylene glycol |
TEMED | N,N,N′,N′-tetramethylethylenediamine |
TEMPO | 2,2,6,6-tetramethylpiperidin-1-oxyl |
TEMPO-NH2 | 4-amino-2,2,6,6-tetramethylpiperidin-1-oxyl |
TFP | tetrafluorophenol |
THPTA | tris-[1-(3-hydroxypropyl)-1H-[1,2,3]triazol-4-yl)methyl]amine |
TMS | trimethylsilyl |
TMSE | 2-(trimethylsilyl)ethyl |
TOM | triisopropylsilyloxymethyl |
TPA | 2,2,5,5-tetramethylpyrrolin-1-yloxyl-3-acetylene |
Tris-HCl | tris(hydroxymethyl)aminomethane hydrochloride |
TSTU | N,N,N′,N′-tetramethyl-O-(N-succinimidyl)uronium tetrafluoroborate |
τm5U | 5-taurinomethyluridine |
τm5s2U | 5-taurinomethyl-2-thiouridine |
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Bartosik, K.; Debiec, K.; Czarnecka, A.; Sochacka, E.; Leszczynska, G. Synthesis of Nucleobase-Modified RNA Oligonucleotides by Post-Synthetic Approach. Molecules 2020, 25, 3344. https://doi.org/10.3390/molecules25153344
Bartosik K, Debiec K, Czarnecka A, Sochacka E, Leszczynska G. Synthesis of Nucleobase-Modified RNA Oligonucleotides by Post-Synthetic Approach. Molecules. 2020; 25(15):3344. https://doi.org/10.3390/molecules25153344
Chicago/Turabian StyleBartosik, Karolina, Katarzyna Debiec, Anna Czarnecka, Elzbieta Sochacka, and Grazyna Leszczynska. 2020. "Synthesis of Nucleobase-Modified RNA Oligonucleotides by Post-Synthetic Approach" Molecules 25, no. 15: 3344. https://doi.org/10.3390/molecules25153344
APA StyleBartosik, K., Debiec, K., Czarnecka, A., Sochacka, E., & Leszczynska, G. (2020). Synthesis of Nucleobase-Modified RNA Oligonucleotides by Post-Synthetic Approach. Molecules, 25(15), 3344. https://doi.org/10.3390/molecules25153344