Cyclic Oligoribonucleotides Research Articles

BRIDGED CYCLIC OLIGORIBONUCLEOTIDES—TOWARDS MODELS FOR CODON-ANTICODON PAIRING

Only three base pairs make up for stable double helices of regular A-type if both helix ends are bridged by flexible non-nucleotide linkers. These cyclic oligoribonucleotides are used as model systems for codon-anticodon pairing in order to reveal base stacking effects arising from structurally relevant bases in the direct neighbourhood of the core triplet duplex.

Bridged Cyclic Oligoribonucleotides as Model Compounds for Codon - Anticodon Pairing R.M. acknowledges the Austrian Academy of Science for an APART fellowship (Austrian Programme for Advanced Research and Technology). This work was supported by the Austrian Science Fund, Vienna (P13216-CHE). R.M. is obliged to Prof. Eschenmoser (Zürich) and Prof. Falk (Linz) for generous hospitality in their laboratories. We thank Dr.

Bridged Cyclic Oligoribonucleotides as Model Compounds for Codon - Anticodon Pairing R.M. acknowledges the Austrian Academy of Science for an APART fellowship (Austrian Programme for Advanced Research and Technology). This work was supported by the Austrian Science Fund, Vienna (P13216-CHE). R.M. is obliged to Prof. Eschenmoser (Zürich) and Prof. Falk (Linz) for generous hospitality in their laboratories. We thank Dr.

ChemInform Abstract: A New Approach to the Synthesis of Linear and Cyclic Oligoribonucleotides

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A new approach to the synthesis of branched and branched cyclic oligoribonucleotides.

The six-step synthesis of the di-triethylammonium salt of 5[prime]-O -trityl-6-N-pivaloyladenosine-2[prime]-(H -phosphonate)-3'-[(2-chlorophenyl) phosphate]9 from 3', 5'- O -(1,1,3,3-tetraisopropyldisiloxan-1,3-diyl)-6-N-pivaloyla denosine1in 68% overall yield is described. Compound9is converted into a branched pentaribonucleoside tetraphosphate 24 and a branched cyclic pentaribonucleotide ('lariat') 25 by solution phase triester chemistry involving both H-phosphonate and conventional phosphotriester coupling reactions. The monomeric building block 9 is proposed as a universal synthon for the preparation of branched and branched cyclic oligoribonucleotides derived from adenosine.

Cyclic Oligoribonucleotides (RNA) by Solid-Phase Synthesis

No restrictions on the sequence variety is one of the key features of the presented solid-phase synthesis for small- to medium-sized cyclic oligoribonucleotides (see diagram). The approach allows fully automated assembly with 2′-O-triisopropylsilyloxymethyl (TOM) RNA phosphoramidites. Ring closure is achieved by standard phosphotriester RNA chemistry. Selective cleavage from the solid support provides the cyclic oligoribonucleotide in high purity after deprotection.

A New Approach to the Synthesis of Linear and Cyclic Oligoribonucleotides

The tetraribonucleoside triphosphate 15 and the cyclic tetraribonucleotide 16 have been prepared by a recently reported triester approach in solution, involving H-phosphonate coupling.

The H-phosphonate approach to the solution phase synthesis of linear and cyclic oligoribonucleotides.

The solution phase synthesis of the tetraribonucleoside triphosphate r(ApCpGpU) 18 and the corresponding cyclic tetraribonucleotide 19 is described. The synthetic methodology is based on 5'- O -(DMTr)-2'- O -(Fpmp)-ribonucleoside-3'- H -phosphonate building blocks 10. Coupling, which is rapid and quantitative, is effected with di-(2-chlorophenyl) phosphorochloridate 5 at -40 degreesC; it is followed by in situ treatment with 2-(4-methyl-phenyl)sulphanyl-1 H -isoindole-1,3(2 H )-dione 6b. The resulting sulphur transfer reaction also proceeds rapidly and quantitatively at -40 degreesC. The same coupling and sulphur transfer steps are used in the cyclization reaction, but a 5'- H -phosphonate intermediate 24 is involved. The final three-step unblocking process involves treatment with (i) E -2-nitrobenzaldoxime 7 and N 1, N 1, N 3, N 3-tetramethylguanidine (TMG) 8 in aceto-nitrile, (ii) concentrated aqueous ammonia at 50 degreesC and (iii) 0.5 mol/dm3sodium acetate buffer (pH 4.0) at 40 degreesC. The fully unblocked products 18 and 19 were characterized by NMR spectroscopy and by enzymatic digestion.

Making cyclic RNAs easily available

A simple solid-phase procedure allows cyclic oligoribonucleotides to be obtained as long as the linear precursor attached to the support has a 2′-deoxyribonucleoside or a 2′-O-methylribonucleoside at the 3′-end.

Design and synthesis of RNA miniduplexes via a synthetic linker approach. 2. Generation of covalently closed, double-stranded cyclic HIV-1 TAR RNA analogs with high Tat-binding affinity.

We recently developed an approach which allows rapid generation of short, double-stranded oligonucleotides whereby one end of the duplex was joined and stabilized by a synthetic linker of specific design (miniduplexes)(6). Model miniduplexes based on the HIV-1 TAR RNA hairpin were shown to be thermodynamically stable and good substrates for binding by the HIV-1 Tat protein which normally bind to natural TAR (6). In this study, we have extended our studies to the design, synthesis and analysis of the binding properties of covalently closed, double-stranded, cyclic RNA miniduplexes. A strategy using automated chemical synthesis and T4 RNA ligase-catalyzed cyclization was employed to generate cyclic oligoribonucleotides. When both ends of a shortened, wild-type TAR RNA stem (9 bp) were covalently linked through either nucleotidic loops (4-6 nt) or synthetic linkers (derivatized from hexaethylene glycol), the resulting cyclic TAR RNA analogs were good substrates for binding by both Tat-derived peptide or full-length Tat protein. Interestingly, the cyclic TAR analogs failed to show any binding if the synthetic linker was reduced in length (e.g. derivatized from triethylene glycol), although such linkers are acceptable in the hairpin-shaped miniduplexes series (6). This implies that RNA conformational changes are required for Tat binding and that these changes are restricted in certain cyclic variants. Our findings suggest that covalently-closed nucleic acid miniduplexes may be useful both to study nucleic acid-protein interactions as well as to provide a basis for therapeutic intervention as transcription decoys.

Facile preparation of cyclic oligoribonucleotides

A convenient solid-phase synthesis of small cyclic oligoribonucleotides based on elongation of the chain by phosphoramidite chemistry, and successive cyclization of the linear fragments by a phosphotriester approach is described.

Studies on transfer ribonucleic acids and related compounds. XXVI. Circular dichroic properties of cyclic oligoribonucleotides and their linear counterparts.

AbstractThe CD spectra of cUpUp, cCpCp, and cGpGp derived from DCC‐catalyzed polymerization of the relevant protected ribonucleoside 3′‐phosphates are described. Similar studies on Up, U > p, and cUp, as well as cUpUpUp and cUpUpUpUp, are presented. The spectral properties of the cyclic oligomers are compared with those of the corresponding linear oligomers with terminal 3′‐phosphates so as to demonstrate that disruption of normal right‐handed base stacking is considerable in these RNA loops.