Preparation of O,O-dimethyl phosphoramidothioate and O,O-dimethyl phosphoroamidothioate. A process of making O,O-dimethyl phosphoroamidothioate is described including reacting sulfur with PCl.sub.3 to form PSCl.sub.3, reacting the PSCl.sub.3 formed with methanol to form O-methyl phosphorodichloridothioate, and reacting the O-methyl phosphorodichloridothioate formed with methyl lye to form O,O-dimethyl phosphorochloridothioate in solution in CH.sub.2Cl.sub.2, and reacting the O,O-dimethyl phosphorochloridothioate formed with sodium hydroxide and ammonium hydroxide to form O,O-dimethyl phosphoroamidothioate in solution in CH.sub.2Cl.sub.2. Reacting the O,O-dimethyl phosphoroamidothioate formed with catalytic dimethyl sulfate to form methamidophos, and reacting the methamidophos formed with acetic anhydride to form N-(methoxy-methylsulfanylphosphoryl) acetamide is also described. Throughout the process, the O,O-dimethyl phosphorochloridothioate and the O,O-dimethyl phosphoroamidothioate formed are maintained in solution in CH.sub.2Cl.sub.2 at all times.

Embodiments of the present disclosure relate to lipid-PEGylated solid support and phosphoramidites derivatives, methods for preparing the same, and their uses in the delivery of oligonucleotide drugs to the cellular targets.

This document relates to functionalized (e.g., mono- or bi-functional) polymers (e.g., polyethylene glycol and related polymers) as well as methods and materials for making and using such functionalized polymers.

The present invention relates to novel hydroxyl compounds, compositions comprising hydroxyl compounds, and methods useful for treating and preventing a variety of diseases and conditions such as, but not limited to aging, Alzheimer's Disease, cancer, cardiovascular disease, diabetic nephropathy, diabetic retinopathy, a disorder of glucose metabolism, dyslipidemia, dyslipoproteinemia, hypertension, impotence, inflammation, insulin resistance, lipid elimination in bile, obesity, oxysterol elimination in bile, pancreatitis, pancreatitius, Parkinson's disease, a peroxisome proliferator activated receptor-associated disorder, phospholipid elimination in bile, renal disease, septicemia, metabolic syndrome disorders (e.g., Syndrome X), thrombotic disorder. Compounds and methods of the invention can also be used to modulate C reactive protein or enhance bile production in a patient. In certain embodiments, the compounds, compositions, and methods of the invention are useful in combination therapy with other therapeutics, such as hypocholesterolemic and hypoglycemic agents.

Compounds useful as fluorescent or colored dyes are disclosed. The compounds have the following structure (II): ##STR00001##
or a stereoisomer, tautomer or salt thereof, wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, L.sup.1, L.sup.2, L.sup.3, L.sup.4, M, m and n are as defined herein. Methods associated with preparation and use of such compounds are also provided.

Disclosed are polynucleotide constructs having a strand linked to a moiety carrying one or more auxiliary moieties. Also disclosed are polynucleotide constructs interrupted with a sugar analogue, and polynucleotide constructs with stereochemical{circumflex over ()} enriched phosphorothioates. The polynucleotide constructs may be provided as hybridized polynucleotide constructs. Also featured are methods of delivery a polynucleotide construct to a cell and methods of reducing the expression of a protein in a cell by contacting the cell with the disclosed polynucleotide construct or hybridized polynucleotide construct.

Disclosed are polynucleotide constructs having a strand linked to a moiety carrying one or more auxiliary moieties. Also disclosed are polynucleotide constructs interrupted with a sugar analogue, and polynucleotide constructs with stereochemical{circumflex over ()}enriched phosphorothioates. The polynucleotide constructs may be provided as hybridized polynucleotide constructs. Also featured are methods of delivery a polynucleotide construct to a cell and methods of reducing the expression of a protein in a cell by contacting the cell with the disclosed polynucleotide construct or hybridized polynucleotide construct.

Compounds are generally provided, along with pharmaceutical compositions including such compounds. Methods are also generally provided for inhibiting ribose 5-phosphate isomerase in a human, such as via administering to the human the pharmaceutical composition that includes such a compound. Methods are also generally provided for treating a mammal that is infected by a parasitic organism, such as via administering to the mammal the pharmaceutical composition that includes such a compound. Methods are also generally provided for forming a pharmaceutical composition.

Compounds of Formula (IA)

(Targeting Moiety)-(Linker)-(Protease Ligand)(IA), where the targeting moiety is an oligonucleotide capable of binding a target protein and the protease ligand is a ligand capable of binding a protease, and methods for the use thereof are provided. Also provided are compounds of Formula (IB)

(Targeting Moiety)-(Linker)-(Protease Ligand or E3 Ligase Ligand)(IB), where the targeting moiety is an oligonucleotide capable of binding a target protein, the protease ligand is a ligand capable of binding a protease, and the E3 ligase ligand is a ligand capable of binding an E3 ligase, and methods for the use thereof are provided.

This is invention is related to processes for synthesis of levoamphetamine derivatives and novel intermediates thereby, and processes for using the same.