239 results about "Phosphoramidite" patented technology

Disclosed is a method of down-regulating the expression of a gene in an animal, wherein a pharmacological formulation comprising a chimeric oligonucleotide complementary to the gene is orally administered to an animal. The oligonucleotide administered has at least one phosphorothioate internucleotide linkage and at least one alkylphosphonate, phosphorodithioate, alkylphosphonothioate, phosphoramidate, phosphoramidite, phosphate ester, carbamate, carbonate, phosphate triester, acetamidate, or carboxymethyl ester internucleotide linkage.

The present invention relates to large scale preparation of LNA phosphoramidites using a 2-cyanoethyl-N,N,N′,N′-tetra-substituted phosphoramidite and a nucleophilic activator, e.g. 2-cyanoethyl-N,N,N′,N′-tetraisopropylphosphoramidite and 4,5-dicyanoimidazole. The method is faster and more cost efficient that previously known methods.

A reagent for oligonucleotide synthesis or purification, wherein the reagent has a structure of:

X—C-L-H  (Formula A)

wherein X is a phosphoramidite group, an H-phosphonate group, an acetal group, or an isocyanate; C is a direct bond or a cleavable adaptor represented by —C_a-C_b—; L is a hydrocarbyl chain; and H is a terminal alkyne or an activated cyclooctyne. The reagent of Formula (A) can be used in the synthesis and purification of oligonucleotides.

Oligonucleotide chemistry is central to the advancement of core technologies such as DNA sequencing, forensic and genetic analysis and has impacted greatly on the discipline of molecular biology. Oligonucleotides and their analogues are essential tools in these areas. They are often produced by automated solid-phase phosphoramidite synthesis but it is difficult to synthesize long DNA and RNA sequences by this method. Methods are proposed for ligating oligonucleotides together, in particular the use of an azide-alkyne coupling reaction to ligate the backbones of oligonucleotides together to form longer oligonucleotides that can be synthesized using current phosphoramidite synthesis methods.

The present invention relates to novel methods and novel solid support materials for the tandem synthesis of two or more different oligonucleotides on the same solid support in one synthetic run. The methods involve novel support preparations comprised of two or more types of orthogonally protected anchor groups. Subsequent to the selective removal of the first of the respective protective groups, the first oligonucleotide is assembled on the deblocked anchor groups according to standard methods, preferably via phosphoramidite chemistry. Following the capping of said first oligonucleotide, the anchor groups blocked by the second type of protective group are selectively liberated and serve is the starting point for the assembly of a second oligonucleotide, and so forth. After completion of all of the syntheses on the solid support, the oligonucleotides are released from the solid support and deprotected at the nucleobases, using standard methods. Preparations obtained using the method of this invention, generally contain two or more different oligonucleotides. Such preparations are particularly useful in applications that require pairs of oligonucleotide primers, several probes at a time, duplexed nucleic acid fragments, or other combinations of oligonucleotides that are useful in applications such as PCR, sequencing, multiplexed genotyping, cloning and RNA interference. The invention includes procedures for the preparation of the novel solid supports of the invention.

The present invention is a microarray having a plurality of subarrays with a hydrophobic barrier that defines each subarray of the microarray, and a method for preparing such a microarray. The hydrophobic barrier is prepared using a microarray synthesis instrument, where NPPOC photoprotected and other hydrophobic group-bearing phosphoramidites are coupled to the microarray using light from a digital micromirror to direct formation of the hydrophobic barrier. The method utilizes hydrophobicity, a well-established property, of conventional phosphoramidite protecting groups for an entirely new application, the synthesis of hydrophobic barriers on microarrays.

Disclosed are novel phosphine-phosphoramidite compounds which may be employed in combination with a catalytically-active metal to effect a wide variety of reactions such as asymmetric hydrogenations, asymmetric reductions, asymmetric hydroborations, asymmetric olefin isomerizations, asymmetric hydrosilations, asymmetric allylations, asymmetric conjugate additions, and asymmetric organometallic additions. Also disclosed are a process for the preparation of the phosphine-phosphoramidite compounds, metal complex compounds comprising at least one of the phosphine-phosphoramidite compounds and a catalytically-active metal and hydrogenation processes utilizing the metal complex compounds.

The present invention relates to processes and reagents for oligonucleotide synthesis and purification. One aspect of the present invention relates to compounds useful for activating phosphoramidites in oligonucleotide synthesis. Another aspect of the present invention relates to a method of preparing oligonucleotides via the phosphoramidite method using an activator of the invention. Another aspect of the present invention relates to sulfur-transfer agents. In a preferred embodiment, the sulfur-transfer agent is a 3-amino-1,2,4-dithiazolidine-5-one. Another aspect of the present invention relates to a method of preparing a phosphorothioate by treating a phosphite with a sulfur-transfer reagent of the invention. In a preferred embodiment, the sulfur-transfer agent is a 3-amino-1,2,4-dithiazolidine-5-one. Another aspect of the present invention relates to compounds that scavenge acrylonitrile produced during the deprotection of phosphate groups bearing ethylnitrile protecting groups. In a preferred embodiment, the acrylonitrile scavenger is a polymer-bound thiol. Another aspect of the present invention relates to agents used to oxidize a phosphite to a phosphate. In a preferred embodiment, the oxidizing agent is sodium chlorite, chloroamine, or pyridine-N-oxide. Another aspect of the present invention relates to methods of purifying an oligonucleotide by annealing a first single-stranded oligonucleotide and second single-stranded oligonucleotide to form a double-stranded oligonucleotide; and subjecting the double-stranded oligonucleotide to chromatographic purification. In a preferred embodiment, the chromatographic purification is high-performance liquid chromatography.

A spirocyclic phosphorous amide is prepared though reaction of spirocyclicdiphenols on substituted phosphorous amide, and features that it has two mutamers: dextro-and levo-spirocyclicphosphorous amides. It can be used for asymmetric catalytic hydrogenating reaction with very high stereo-selectivity (more than 99% of e.e. value).

A process of purifying phosphoramidite precursors useful in inter alia synthesis of oligonucleotides comprises dissolving a crude phosphoramidite in a polar phase, adding a basic compound to the polar phase, adding a portion of water to the polar phase, contacting the polar phase with a first apolar phase to extract impurity into the apolar phase, separating the first apolar phase from the polar phase, adding a second aliquot of water to the polar phase, and contacting the polar phase with a second apolar phase, whereby the phosphoramidite partitions into the second apolar phase.

The present invention relates generally to nucleic acid chemistry and to the chemical synthesis of oligonucleotides. More particularly, the invention relates to improved methods for synthesizing oligonucleotides wherein periodate salts are used (e.g., in organic solvents) as an oxidation reagent in oligonucleotide synthesis (e.g., for automated phosphoramidite synthesis of oligonucleotides). The invention finds utility in the fields of biochemistry, molecular biology, and pharmacology, and in medical diagnostic and screening technologies.

The present invention discloses a kit and method for modifying vitro synthesized RNA, particular: (1) in chemical synthesis of RNA, using phosphoramidite monomer with 1, 3-di-dipole group or pro-dipole group to synthesis ribonucleic acid; (2) the after or during the synthetic process, modified ribonucleic acid and corresponding pio-dipole group or biomolecular probe of the 1, 3-di-dipole group performing 'click' reaction at the present of cuprous ion compounds catalyst, the ribonucleic acid is modified. The present invention provided kit and method for modifying RNA avoid shortcomings of traditional molecule connecting method active molecule decomposition and inactivation in RNA synthesis or doff protecting group process. The invention is provided with advantages of low cost, simple operation, mild condition, good modify impression and will not affect biological activity of any RNA.

This invention relates to nucleoside, nucleotide, and oligonucleotide analogs that incorporate non-standard nucleobase analogs, defined to be those that present a pattern of hydrogen bonds to a paired nucleobase analog in a complementary strand that is different from the pattern presented by adenine, guanine, cytosine, and thymine. The invention is specifically concerned with nucleotide analogs that present the donor-donor-acceptor, hydrogen bonding patterns on pyrimidine analogs, and especially those that are analogs of ribonucleotides, including protected ribonucleotides suitable for phosphoramidite-based synthesis of RNA. The heterocycles on these nucleoside analogs are aminopyridones that have electron withdrawing groups attached to the position analogous to the 5-position of the ring in standard pyrimidines, including nitro, cyano, and carboxylic acid derivatives.