Abstract: Phosphoramidate esters and related nucleotide analogs useful in polynucleotide sequencing techniques, and synthetic methods for preparing those compounds, are disclosed, including compounds having the following structure: wherein R1, R2, R3 and R4 are as defined herein.

Abstract: The invention relates to a recognizable carrier for determining physical, chemical or biochemical interactions by means of optical measurement methods. The carrier comprises a surface that defines a substrate surface and that has a base layer coated with reactive elements, which are bonded to receptor molecules, wherein the base layer and/or the reactive elements are provided with a pattern of holes which forms a code and/or the reactive elements are provided with linker molecules or markers which form a code. The substrate surface may additionally have a macroscopically planar pattern which is applied using laser light or chemical etching and forms a code. The invention likewise relates to a method for producing a recognizable carrier for spectroscopic processes and/or intensiometric tests to determine said interactions. The code to recognize the carrier can be controlled via a read-out unit coupled to the photometric analysis unit.

Abstract: Disclosed herein are compositions and methods for generating ribo-nucleic neutral (RNN) or deoxyribo-nucleic-neutral (DNN) polynucleotides with reduced anionic charge, for improved intracellular delivery. Also disclosed herein are methods of using RNN and DNN compositions.

Abstract: The invention provides compositions of oligonucleotides targeted at influenza genes and at host animal genes involved in response to influenza infection. In some embodiments, the oligonucleotides are modified. In some embodiments, the compositions contain one, or more than one, oligonucleotide. The invention also provides methods and kits using the compositions of the invention for the treatment and prevention of influenza.

Abstract: The present invention provides compositions methods for treating susceptible viral infections, especially hepatitis C viral (HCV) infections as well as co infections of HCV with other viruses such as HBV and/or HIV. In one embodiment, the present invention provides compositions having the formula (I) and their use in treating viral infections: or a pharmaceutically acceptable salt, ester, stereoisomer, tautomers, solvate, prodrug, or combination thereof.

Abstract: An oligonucleotide derivative having the structure of formula (A) and methods for preparing the oligonucleotide derivative are disclosed. wherein R3 is a first oligonucleotide; R1 is selected from the group consisting of alkyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, a polyethylene glycol, a peptide, a protein, a polysaccharide, and a second oligonucleotide; R2 is a linker or a direct bond; Z1 is NR4, S, or O, and Z2 is NR4 or S, wherein R4 is selected from H, alkyl, aryl, heterocyclyl, or heteroaryl. A method includes: synthesizing an oligonucleotide derivative comprising an amino or thiol group; and reacting a 3,4-dialkoxycyclobutene-1,2-dione with the oligonucleotide derivative to produce an oligonucleotide-squarate mono-conjugate.

Abstract: Methods and compounds are disclosed for irreversibly inhibiting a DNA repair enzyme that possesses lyase activity.

Abstract: Provided herein are novel bicyclic nucleosides, oligomeric compounds that include such bicyclic nucleosides and methods of using the oligomeric compounds. More particularly, the novel bicyclic nucleosides comprise a furanose ring system having a bridge comprising a 4?-methylene group attached to a 2?-sulfoxide or sulfone group and optionally including one or more substituent groups attached to the 4?-methylene and or the 5?-position. In certain embodiments, the oligomeric compounds provided herein are expected to hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA.

Abstract: An agent for inhibiting translesion DNA replication comprises a non-natural adenine ribose analog represented by those as set forth in FIG. 1.

Abstract: Alkynyl-derivatized cap analogs, alkynyl-modified capped RNA, 1,4-disubstituted triazole-derivatized capped RNA, methods of preparation, methods of isolation, and uses thereof are provided. The “click” modification facilitates detection and isolation of capped RNAs and the 1,4-disubstituted triazole derivatives formed by the “click” reaction are useful for producing RNA transcripts and encoded protein.

Abstract: The invention features compounds of formula I or II: In one embodiment, the invention relates compounds and processes for conjugating ligand to oligonucleotide. The invention further relates to methods for treating various disorders and diseases such as viral infections, bacterial infections, parasitic infections, cancers, allergies, autoimmune diseases, immunodeficiencies and immunosuppression.

Abstract: The present invention provides novel 3?,5?-linked bicyclic nucleosides and oligomeric compounds prepared therefrom. The bicyclic nucleosides provided herein are useful for enhancing one or more properties of the oligomeric compounds they are incorporated into such as nuclease resistance.

Abstract: The present invention includes compounds and compositions of ®-2?-fluoronucleoside phosphonates, as well as methods to treat HIV, HBV, HCV or abnormal cellular proliferation comprising administering said compounds or compositions.

Abstract: Disclosed herein are phosphorus-containing actives, their use as actives for treating diseases, and a stereoselective process for preparing the same. Also disclosed herein are useful synthetic intermediates and processes for preparing the same.

Abstract: Nucleoside phosphinoamidite carboxylates and analogs are provided that have the structure of formula (III) wherein A is hydrogen, hydroxyl, lower alkoxy, lower alkoxy-substituted lower alkoxy, halogen, SH, NH2, azide or DL wherein D is O, S or NH and L is a heteroatom-protecting group, unsubstituted hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, or substituted heteroatom-containing hydrocarbyl; B is a nucleobase; and one of R11 and R12 is a blocking group and the other is (IV) or (VI) in which W, X, Y, Z, R1 and n are as defined herein.

Abstract: This invention relates to n-alkylated synthetic nucleosides and phosphoramidites of high regio-specific purity and stability and for selective deprotection of the protecting group in oligonucleotides for the purpose of synthesis of high purity selectively n-alkylated sequence specific DNA and RNA. Such oligonucleotides are useful for study of mechanism of cytotoxic and mutagenic DNA damage, detection and reversal of cellular cytotoxic and mutagenic damages that occurs from the incorporation of methylated nucleosides, the corresponding phosphates and triphosphates and their precursors, via de novo DNA synthesis. The reagents could be extremely valuable tools as diagnostics and mutagenic reversal reagents.

Abstract: The invention provides a compound of formula (I), wherein R1-R6 and X have any of the values described, as well as pharmaceutical compositions comprising such compounds and therapeutic methods comprising the administration of such compounds.

Abstract: A protecting group for 1-nitrogen atom of an indole group including a sulfonylethyl carbamate group, wherein the protecting group is represented by the following General Formula (I) and capable of being removed from the 1-nitrogen atom of the indole group in an aprotic solvent: where R represents an alkyl group, a derivative of the alkyl group, a phenyl group or a derivative of the phenyl group.

Abstract: Cyclic phosphate of nucleoside derivatives for the treatment of viral infections in mammals, which is a compound, its stereoisomers, salts (acid or basic addition salts), hydrates, solvates, or crystalline forms thereof, represented by the following structure:

Abstract: A process for preparing phosphoramidate prodrugs or cyclic phosphate prodrugs of nucleoside derivatives, which is a compound, its stereoisomers, salts (acid or basic addition salts), hydrates, solvates, or crystalline forms thereof.

Abstract: Disclosed herein are compositions and methods for generating ribo-nucleic neutral (RNN) or deoxyribo-nucleic-neutral (DNN) polynucleotides with reduced anionic charge, for improved intracellular delivery. Also disclosed herein are methods of using RNN and DNN compositions.

Abstract: An object of the present invention is to provide a useful and novel phosphoramidite compound for the synthesis of oligo-RNA. A phosphoramidite compound represented by general formula (1), wherein: BX represents a nucleobase optionally having a protecting group; and R1 is a substituent represented by general formula (2), wherein: R11, R12 and R13 are the same or different and each represents hydrogen or alkoxy; R2a and R2b are the same or different and each represents alkyl, or R2a and R2b taken together with the adjacent nitrogen atom may form a 5- to 6-membered saturated amino cyclic group, the amino cyclic group optionally having an oxygen or sulfur atom as a ring-composing member in addition to the adjacent nitrogen atom; and WG1 and WG2 are the same or different and each represents an electron-withdrawing group.

Abstract: A bifunctional linker and method of use is provided that has a spacer molecule with a functional group on one end configured to couple to the surface of a substrate and a function group on the other end that is configured couple to a biomolecule and methods of use. The preferred bifunctional linker has a poly(ethylene glycol) spacer ranging from 3 to 20 ethylene glycol units that has a silane functional group to react with a substrate and an azide functional group that can couple to a biomolecule that includes an alkyne group. The preferred linker can produce an azide-derivatized glass surface in one step and the azide functional group of the spacer can in sequence conjugate with a biomolecule using click chemistry, which can be conducted at low temperature and in aqueous solution.

Abstract: Methods, Compositions, and Systems are provided for nucleic acid sequencing where the sequential incorporation of nucleotides uses two distinct chemical steps. A plurality of nucleotide analogs, each having a labeled leaving group at its 3? hydroxyl can be sequentially added to a growing strand in the presence of a selective cleaving activity that cleaves the 3? hydroxyl leaving group preferentially after it has been incorporated. The selective cleaving agent can comprise an exonuclease activity, and the exonuclease activity can be a polymerase-associated exonuclease activity. Nucleotide analogs having labels on both a cleavable polyphosphate portion and on a 3? hydroxyl leaving group can provide signals characteristic of nucleotide analog incorporation. Systems having illumination optics, collection optics, and substrates observe signals from the labels as they are being incorporated into a growing nucleic acid strand, allowing for the sequencing of template nucleic acids.

Abstract: Liquid microbial starter culture that retains its initial metabolic activity during storage for extended periods of time. Such liquid starter cultures are useful in the manufacturing of food and feed products. Starter cultures of the invention include culture of lactic acid bacteria, e.g. Lactococcus species.

Abstract: We disclose here a method for using Poly-ICLC to prevent and/or treat certain human and veterinary infectious, neoplastic and autoimmune disorders, as well as for regulating a broad variety of genes in humans, consisting of use of poly-ICLC repeatedly and at low doses, alone or in combination with other drugs or vaccines. As such it represents an example of broad spectrum host-targeted therapeutics, in contrast to conventional antibiotics, antiviral or antineoplastic agents that target specific organisms or tumors.

Abstract: A modified compound that has at least one further functional group, in particular a bio- or macromolecule, comprising at least one x-fold (x?1) chemoselectively incorporated phosphoramidate group of general formula (I), NPO(OR1)(OR1?), and/or at least one x-fold (x?1) chemoselectively incorporated phosphonamide group of general formula (Ia), NPO(R1)(OR1?). R1 and R1? is selected from the group containing glycerol, polyglycerol, PEG polymers of the general empirical formula C2nH4n+2On+1 with n?1, Cn-alkyl chains with n?1; functionalized Cn-alkyl chains with n?1, aryls, heteroaryl, silyl, lipids, fluorophores, saccharides, peptides, crown ethers, or a linker, which links the aforementioned groups. R1 and R1? can be identical to or different from one another.

Abstract: The present invention relates to 2?-chloroacetylenyl-substituted nucleoside derivatives of the general formula (I): As well as pharmaceutical compositions comprising such compounds and methods to treat or prevent an HIV infection, HBV infection, HCV infection or abnormal cellular proliferation, comprising administering said compounds or compositions. In addition, the present invention includes processes for the preparation of such compounds, and the related ?-D and ?-L-nucleoside derivatives.

Abstract: A purified compound having activity against hepatitis C virus is disclosed.

Abstract: The present invention provides novel carbocyclic ?-L-bicyclic nucleosides and oligomeric compounds comprising at least one of these carbocyclic ?-L-bicyclic nucleosides. The carbocyclic ?-L-bicyclic nucleosides are useful for enhancing one or more properties of the oligomeric compounds they are incorporated into including nuclease resistance.

Abstract: Compounds used as labels with properties comparable to known fluorescent compounds. The compounds can be conjugated to proteins and nucleic acids for biological imaging and analysis. Synthesis of the compounds, formation and use of the conjugated compounds, and specific non-limiting examples of each are provided.

Abstract: Therapeutic conjugates containing a statin or a modified statin (collectively “statin”) linked to a therapeutic agent (also referred to as a drug herein) are targeted to the liver by the statin or modified statin and thereby deliver the therapeutic agent to liver cells

Abstract: The invention provides modified nucleotide or nucleoside molecule comprising a purine or pyrimidine base and a ribose or deoxyribose sugar moiety having a removable 3?-OH blocking group covalently attached thereto, such that the 3? carbon atom has attached a group of the structure —O—Z wherein Z is any of —C(R?)2-O—R?, —C(R?)2-N(R?)2, —C(R?)2-N(H)R?, —C(R?)2-S—R? and —C(R?)2-F, wherein each R? is or is part of a removable protecting group; each R? is independently a hydrogen atom, an alkyl, substituted alkyl, arylalkyl, alkenyl, alkynyl, aryl, heteroaryl, heterocyclic, acyl, cyano, alkoxy, aryloxy, heteroaryloxy or amido group, or a detectable label attached through a linking group; or (R?)2 represents an alkylidene group of formula ?C(R??)2 wherein each R?? may be the same or different and is selected from the group comprising hydrogen and halogen atoms and alkyl groups; and wherein said molecule may be reacted to yield an intermediate in which each R? is exchanged for H or, where Z is —C(R?) 2-F, the F is e

Abstract: The present invention relates to prodrug forms of ?-L-1-[5-(E-2-Bromovinyl)-2-(hydroxymethyl)-1,3-dioxolan-4-yl)]uracil (L-BHDU) and their use to treat viral infections of Varicella Zoster Virus, including recurrent VZV (shingles), especially including drug resistant Varicella Zoster Virus and related complications of this viral infection such as rash or post-herpetic neuralgia.

Abstract: The present invention provides iRNA agents comprising at least one subunit of the formula (I): wherein: A and B are each independently for each occurrence O, N(RN) or S; X and Y are each independently for each occurrence H, OH, a hydroxyl protecting group, a phosphate group, a phosphodiester group, an activated phosphate group, an activated phosphite group, a phosphoramidite, a solid support, —P(Z?)(Z?)O-nucleoside, —P(Z?)(Z?)O-oligonucleotide, a lipid, a PEG, a steroid, a lipophile, a polymer, —P(Z?)(Z?)O-Linker-OP(Z??)(Z??)O-oligonucleotide, a nucleotide, an oligonucleotide, —P(Z?)(Z?)-formula (I), —P(Z?)(Z?)— or -Linker-R; R is LG, -Linker-LG, or has the structure shown below: LG is independently for each occurrence a carbohydrate, e.g.

Abstract: The invention provides analogs cyclic diguanosine monophosphate (c-di-GMP) having different substituents at the guanine C8 position.

Abstract: The invention relates to analogous compounds of 6-thioguanosine triphosphate of general formula (I). A compound of the general formula (I); wherein the dashed bond in the sugar moiety can be either single or double and wherein R1, R2, R3, R4 or R5, equal or different between each other, have general formula -(Int)m-Ter, wherein m is between 0 and 12 and Int and Ter are Internal and Terminal building blocks, wherein Int is selected from the group consisting of formula (II); and Ter is selected from the group consisting of formula (III).

Abstract: The invention provides a compound of formula (I), wherein R1-R6 and X have any of the values described, as well as pharmaceutical compositions comprising such compounds and therapeutic methods comprising the administration of such compounds.

Abstract: Compositions and methods comprising bioenergetic agents for restoring the quality of aged oocytes, enhancing oogonial stem cells or improving derivatives thereof (e.g., cytoplasm or isolated mitochondria) for use in fertility-enhancing procedures, are described.

Abstract: Provided herein are novel 5?-(S)—CH3 substituted bicyclic nucleosides, oligomeric compounds prepared therefrom and methods of using the oligomeric compounds. More particularly, the furanose ring of each of the novel 5?-(S)—CH3 substituted bicyclic nucleosides includes a 2? to 4? bridging group. The 5?-(S)—CH3 substituted bicyclic nucleosides are expected to be useful for enhancing one or more properties of the oligomeric compounds they are incorporated into such as for example increasing the binding affinity. In certain embodiments, the oligomeric compounds provided herein hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA.

Abstract: Provided are novel nucleotides, nucleoside, and their derivatives described herein, that can be used in DNA sequencing technology and other types of DNA analysis. In one embodiment, the nucleotide or nucleoside with an unprotected 3?-OH group is derivatized at the nucleobase to include a fluorescent dye attached via a linker to a photocleavable terminating group. The photocleavable-fluorescent group is designed to terminate DNA synthesis as well as be cleaved so that DNA oligomers can be sequenced efficiently in a parallel format. The design of such rapidly cleavable fluorescent groups on nucleotides and nucleosides can enhance the speed and accuracy of sequencing of large oligomers of DNA in parallel, to allow rapid whole genome sequencing, and the identification of polymorphisms and other valuable genetic information, as well as allowing further manipulation and analysis of nucleic acid molecules in their native state following cleavage of the fluorescent group.

Abstract: This invention describes a simple method useful for the excision and isolation of maize immature embryos. The embryos are useful for plant tissue culture and transformation methods.

Abstract: Compounds used as labels with properties comparable to known fluorescent compounds. The compounds can be conjugated to proteins and nucleic acids for biological imaging and analysis. Synthesis of the compounds, formation and use of the conjugated compounds, and specific non-limiting examples of each are provided.

Abstract: Novel cap analogs which are easily synthesized, resulting in high levels of capping efficiency and transcription and improved translation efficiencies are provided. Such caps are methylated at the N7 position of one or both guanosines of the dinucleotide cap as well as at the 3? position on the ribose ring. Substituent groups on the ribose ring also result in the cap being incorporated in the forward orientation. Also provided are methods useful for preparing capped analogs and using mRNA species containing such analogs are also contemplated herein, as well as kits containing the novel cap analogs.

Abstract: The present disclosure describes 6-disubstituted bicyclic nucleosides, oligomeric compounds prepared therefrom and methods of using the oligomeric compounds. More particularly, the 6-disubstituted bicyclic nucleosides each comprise a 2?-O—C(Ri)(R2)-4? or 2?-O—C=(R3)(R.4)-4? bridge wherein each R is, independently a substituent group and Ri and R2 include H. The 6-disubstituted bicyclic nucleosides are useful for enhancing properties of oligomeric compounds including nuclease resistance. In certain embodiments, the oligomeric compounds provided herein hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA.

Abstract: Provided herein are bicyeMc nucleosides comprising a substituted amino group in the bridge, oligomeric compounds having at least one of these bicyclic nucleosides and methods of using the oligomeric compounds. The bicyclic nucleosides comprising a substituted amino group in the bridge are useful for enhancing properties of oligomeric compounds including nuclease resistance, in certain embodiments, the oligomeric compounds hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA.

Abstract: Provided herein are saturated and unsaturated carbocyclic bicyclic nucleosides, oligomeric compounds prepared therefrom and methods of using these oligomeric compounds. The saturated and unsaturated carbocyclic bicyclic nucleosides are useful for enhancing properties of oligomeric compounds including nuclease resistance.

Abstract: The present invention relates to 2?-allene-substituted nucleoside derivatives of the general formula (I): As well as pharmaceutical compositions comprising such compounds and methods to treat or prevent an HIV infection, HBV infection, HCV infection or abnormal cellular proliferation, comprising administering said compounds or compositions. In addition, the present invention includes processes for the preparation of such compounds, and the related ?-D and ?-L-nucleoside derivatives.

Abstract: The present invention provides 5?-modified bicyclic nucleoside analogs and oligomeric compounds comprising at least one of these nucleoside analogs. In preferred embodiments the nucleoside analogs have either (R) or (S)-chirality at the 5?-carbon. These bicyclic nucleoside analogs are useful for enhancing properties of oligomeric compounds including for example enhanced nuclease resistance.

Abstract: The present patent application relates to the novel nucleoside derivatives and novel intermediates, which are useful to antiviral, anti tumor and immunomodulatory activity, method of treating diseases, conditions and/or disorders modulated by viral infections with them, and processes for preparing them.