25 results about "Y nucleoside" patented technology

The present disclosure relates to methods of treating certain diseases and disorders (e.g., cancer) with a combination of an IRAK4 inhibitor, a BCL-2 inhibitor, and a nucleoside analog.

The present disclosure relates to 4'-thio-nucleotides and nucleoside compounds for the treatment of various cancers, such as, for example, sarcomas, carcinomas, hematological cancers, solid tumors, breast cancer, cervical cancer, gastrointestinal cancer, colorectal cancer, brain cancer, skin cancer, prostate cancer, ovarian cancer, bladder cancer, thyroid cancer, testicular cancer, pancreatic cancer, endometrial cancer, melanoma, glioma, leukemia, lymphoma, chronic myeloproliferative disorder, myelodysplastic syndrome, myeloproliferative tumors and plasma cell neoplasms (myeloma). The abstract is intended to be a scanning tool for the purpose of searching in a specific field and is not intended to limit the present invention.

Disclosed herein are improved methods and compositions of de novo synthesis of nucleic acids by cyclic extension using nucleotides that have an N-linked or O-linked scar or protecting group, and subsequent removal of the scar or protecting group. During polymerase-nucleotide conjugate-based polynucleotide synthesis or after the synthesis is completed, nucleobases having a scar from linker cleavage can be converted back into native form by removal of the scars from the nucleobases. Secondary structure formation in the nascent chain, which may inhibit extension reactions, is suppressed by the use of monomers with protected nucleobases that prevent Watson-Crick base pairing and / or other structures. After the synthesis is completed, the nucleobases can be converted back into native form by palladium-based removal of the protecting groups.

The present disclosure relates to nucleotide and nucleoside therapeutic compositions and uses in the treatment of infectious diseases, viral infections, and cancer, wherein the base of the nucleotide or nucleoside contains at least one thiol, thione, or thioether.

This disclosure related to nucleotide and nucleoside therapeutic compositions and uses in treating infectious diseases, viral infections, and cancer, where the nucleotide or nucleoside is a compound having the formula:

Provided are: a method for producing a compound useful as a nucleotide prodrug; a compound useful as a starting material or an intermediate of the production method; and a nucleotide prodrug precursor.　A method for producing a compound according to the present invention comprises: an aryloxylation step for reacting a compound (1) with a phenol compound ArOH to obtain a compound (2); an oxidative halogenation step for oxidatively halogenating the compound (2) with a halogenating agent to obtain a compound (3); and an amination step for reacting the compound (3) with a compound (5) to obtain a compound (4). In the formula, R11-R15 are a hydrogen atom, etc., R1 is an optionally substituted aryl group, R2-R4 are a hydrogen atom, etc., R5 is an optionally substituted alkyl group, R6 is an amino acid side chain, etc., Ar is an optionally substituted aryl group, X is a halogenyl group, A- is a counter anion, and Bs represents a nucleic acid base optionally having a protecting group.

The present disclosure provides single or double stranded interfering RNA molecules (e.g., siRNAs) that target a transmembrane 4 domain AGA (MS4A6A) gene. The interfering RNA molecule may contain a specific pattern of nucleoside modification and inter-nucleoside linkage modification as a pharmaceutical composition comprising the interfering RNA molecule. The siRNA molecule may be a branched siRNA molecule, such as a two-branched, three-branched or four-branched siRNA molecule. The disclosed siRNA molecules may also be characterized by a 5 '-phosphorus stabilizing moiety and / or a hydrophobic moiety. In addition, the present disclosure provides methods for delivering the siRNA molecules of the present disclosure to a subject, such as the central nervous system of a subject identified as having a neuroinflammatory disease (e.g., Alzheimer's disease).

This disclosure relates to nucleotide and nucleoside therapeutic compositions and their use in treating infectious diseases, viral infections and cancer, wherein the bases of said nucleotide or nucleoside contain at least one thiol, thion, or thioether.

The present disclosure relates to novel nucleotide precursors and nucleotide analogs that can be incorporated into oligonucleotides, including double-stranded oligonucleotides, such as siRNA. Oligonucleotides containing these analogs have excellent biological activity, for example, increased in vitro stability and improved in vivo efficacy, particularly duration of action. Improved oligonucleotides can be used to silence (e.g., reduce or eliminate) the expression of target genes. In a specific embodiment, the present invention encompasses specific nucleotide analogs to be included in double-stranded RNA (dsRNA) and especially siRNA, which can hybridize with the messenger RNA (mRNA) of interest, thereby reducing or blocking the expression of the target gene of interest. The compounds of the present invention have the general formula (I), wherein Ra, Rb, Rc, and Rd are each independently H or (C1-C6) alkyl, and B is a heterocyclic nucleobase. #imgabs0#

The purpose of the present invention is to provide an alkylating agent capable of alkylating a hydroxyl group at the 2 '-position of a synthetic intermediate of an AMIDITE compound in the presence of a base. The present invention provides an alkyl halide represented by general formula (I) capable of alkylation in the presence of a base. In the formula, X represents a halogen atom; n represents an integer of 1-5; r1 and R2 are the same or different and represent a methyl group, an ethyl group or a hydrogen atom; eWG represents a cyano group or a SO2R3 group, and R3 represents a phenyl group optionally substituted by a halogen atom, a methyl group, a nitro group, a methoxy group or a trifluoromethyl group, an alkyl group having 1-10 carbon atoms, or a benzyl group. # imgabs0 #

Provided herein is a one-pot method of synthesising a C-nucleoside-5′-monophosphate such as pseudouridine-5′-monophosphate, from an N-nucleoside using a multi-step enzymatic pathway. The method comprises reacting the N-nucleoside with a phosphate source and nucleoside phosphorylase to form a pentose-1-phosphate intermediate, reacting the pentose-1-phosphate intermediate with a phosphomutase to form pentose-5-phosphate intermediate, and reacting the pentose-5-phosphate intermediate with a nucleoside-5′-phosphate C-glycosidase to form the C-nucleoside-5′-monophosphate.

The present invention discloses methods and intermediates for synthesizing nucleosides and nucleoside analogs (NAs). More specifically, the present invention discloses methods for synthesizing nucleosides and NAs using simple achiral materials through a "one-step" proline-catalyzed halogenation reaction of heteroaryl-substituted acetaldehydes, followed by a tandem enantioselective aldol condensation reaction, and then a reduction or organometallic addition and cyclization (cyclization) reaction, including a cyclization halide displacement reaction.

The invention relates to the technical field of chemical synthesis, in particular to an oligonucleotide-terminated N-acetylgalactosamine modified pentaerythritol derivative, a preparation method thereof, a delivery compound and a nucleotide drug. The N-acetylgalactosamine modified pentaerythritol ether derivative is selected from compounds shown in the following structural formula: # imgabs0 #, X is H or a hydroxyl protecting group, Y is an amino protecting group, A, B and C are independently selected from linking groups formed by at least one of a hydrogen element, a carbon element, an oxygen element, a sulfur element and a phosphorus element respectively, and D is a linking group for solid-phase synthesis of oligonucleotide. The compound can be used as an end-capping reagent of oligonucleotides, can be bonded with the oligonucleotides, and then can be used for delivering drugs so as to realize RNAi (Ribonucleic Acid Interference) therapy.

Compounds, methods, and compositions for treating or preventing viral infections using nucleoside compounds. The nucleoside compounds have increased antiviral activity potential with the result of inhibiting at least one of flaviviruses, herpesviruses, polyomaviruses, alphaviruses, enteroviruses, filoviruses matonaviruses, phenuiviruses, Hepatitis B virus, and / or coronaviruses.

The present disclosure provides single-stranded or double-stranded interfering RNA molecules (e.g., siRNAs) that exhibit improved gene silencing. The present disclosure provides siRNA molecules having a fixed nucleobase region. For example, the antisense strand of the siRNA molecule may have a nucleobase region containing one or more mismatches relative to a target mRNA molecule. Alternatively or additionally, the antisense strand may contain a nucleobase region having a sequence independent of the target mRNA. An immobilization region may be included within a protruding end region of the antisense strand. The siRNA molecule may contain a specific pattern of nucleoside modification and a nucleoside-to-nucleoside linkage modification, as a pharmaceutical composition comprising the siRNA molecule. The siRNA molecule may be a branched siRNA molecule, such as a two-branched, three-branched or four-branched siRNA molecule. The disclosed siRNA molecules may further be characterized by a 5 '-phosphorus stabilizing moiety and / or a hydrophobic moiety. In addition, the present disclosure provides methods for delivering siRNA molecules of the present disclosure to a subject, such as the central nervous system of a subject identified as having a neurodegenerative disease.

In one aspect, the invention relates to a TnpB variant polypeptide comprising a Deinococcus radiodurans (ISDra2) TnpB polypeptide sequence and, separated by a peptide linker, a nuclear localization module comprising at least two nuclear localization sequences (NLS) separated by a first peptide linker. A second aspect of the invention relates to a DNA editing polypeptide comprising the TnpB variant polypeptide according to the invention, wherein the TnpB variant polypeptide comprises a nuclease deactivating mutation, and a nucleoside deaminase. The invention further relates to a nucleic acid sequence encoding a polypeptide according to the invention, and to a virus comprising the nucleic sequence.

Provided herein is a one-pot method for synthesizing a C-nucleoside-5'-monophosphate, such as pseudouridine-5'-monophosphate, from an N-nucleoside using a multi-step enzymatic pathway, comprising reacting the N-nucleoside with a phosphate source and a nucleoside phosphorylase to form a pentose-1-phosphate intermediate, reacting the pentose-1-phosphate intermediate with a phosphomutase to form a pentose-5-phosphate intermediate, and reacting the pentose-5-phosphate intermediate with a nucleoside-5'-phosphate C-glycosidase to form the C-nucleoside-5'-monophosphate.

Disclosed herein compositions comprising at least two siRNAs connected to each other by a multivalent linker, wherein at least one of the at least two siRNAs comprise at least one modified inter-nucleoside linkage, at least one modified nucleoside, or a combination thereof. The at least one siRNA provided herein can be used to target and reduce expression of a gene encoding angiopoietin-like protein, such as angiopoietin-like protein 4 (also referred to as ANGPLT4). Various modifications to inter-nucleoside linkage and nucleoside are also disclosed. The compositions provided herein can be used to treat diseases, conditions, and reduce or maintain body weight in a subject.

Embodiments of the present disclosure relate to modified adenosine nucleosides and nucleotides. Also provided herein are methods and kits for sequencing applications using such nucleotides.

This disclosure relates to nucleotide and nucleoside therapeutic compositions and uses in treating infectious diseases, viral infections, and cancer, where the base of the nucleotide or nucleoside contains at least one thiol, thione or thioether. The nucleotide and nucleoside therapeutic compositions can include at least one second antiviral agent, such as an antiviral agent that treats or prevents enterovirus infections.

The present invention relates to a nucleoside or nucleotide comprising a nucleobase attached to a detectable label via a cleavable linker wherein the nucleoside or nucleotide comprises a ribose or 2'deoxyribose moiety and a 3 '-OH capping group, and wherein the cleavable linker comprises a moiety having the structure (I) wherein X and Y are each independently O or S; and Rla, R2b, R2, R3a, and R3b are each independently H, a halogen, an unsubstituted or substituted C1-C6 alkyl group, or a C1-C6 haloalkyl group. Also provided herein are methods of making such nucleotide molecules and nucleoside molecules, and the use of fully functionalized nucleotides containing 3 'acetal capping groups for sequencing applications. # imgabs0 #

This disclosure relates to therapeutic compositions of nucleotides and nucleosides and their use in the treatment of infectious diseases, viral infections and cancer, where the base of the nucleotide or nucleoside contains at least one thiol, thione or thioether.

This disclosure relates to nucleotide and nucleoside therapeutic compositions and uses in treating infectious diseases, viral infections, and cancer, where the base of the nucleotide or nucleoside contains at least one thiol, thione or thioether.

Embodiments of the present disclosure relate to modified adenosine nucleosides and nucleotides. Also provided herein are methods and kits for sequencing applications using such nucleotides.

The present invention features bifunctional, soluble ecto-enzymes that are engineered to hydrolyze extracellular nucleotide triphosphates (e.g., ATP) to a nucleoside (e.g., adenosine), through the fusion of the ectodomains (ECD) of an ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase) and a nucleotide monophosphatase (NMPAse), such as an ecto-5′ nucleotidase (eN), alkaline phosphatase (ALP), or an acid phosphatase (AP). Also described are methods of use thereof, e.g. for limiting and decreasing inflammation and sequelae.