200133-16-0

Upstream product

• 200133-20-6 di-tert-butyl 3,3'-((2-(((benzyloxy)carbonyl)amino)-2-((3-(tert-butoxy)-3-oxopropoxy)methyl)propane-1,3-diyl)bis(oxy))dipropionate 
• 220431-66-3 benzyl N-{tris[2-(ethoxycarbonyl)ethoxymethyl]methyl}carbamate 
• 132491-90-8 3-[2-Amino-3-(2-ethoxycarbonyl-ethoxy)-2-(2-ethoxycarbonyl-ethoxymethyl)-propoxy]-propionic acid ethyl ester 
• 175724-30-8 tris{[2-(tert-butoxycarbonyl)ethoxy]methyl}methylamine 
• 501-53-1 benzyl chloroformate 
• 166047-75-2 tris[(carboxyethoxy)ethyl](amino)methane trimethyl ester 
• 132491-89-5 tris(cyanoethoxymethyl)aminomethane 
• 200133-15-9 N-(Benzyloxycarbonyl)-tris[((methoxycarbonyl)ethoxy)methyl]aminomethane 

Downstream Products

• 220431-66-3 benzyl N-{tris[2-(ethoxycarbonyl)ethoxymethyl]methyl}carbamate 
• 490040-40-9 C₆₃H₉₈N₁₀O₂₀ 
• 849114-67-6 benzyl N-tris{[2-(2,3,4,5,6-pentachlorophenoxycarbonyl)ethoxy]methyl}methyl carbamate 
• 651354-67-5 {2-[2-(2-tert-butoxycarbonylaminoethylcarbamoyl)-ethoxy]-1,1-bis-[2-(2-tert-butoxycarbonylamino-ethylcarbamoyl)-ethoxymethyl]-ethyl}-carbamic acid benzyl ester 
• 956347-51-6 C₁₃₅H₂₁₈N₁₆O₄₄ 
• 1162069-31-9 3-[2-(benzyloxycarbonylamino)-3-(2-carboxyethoxy)-2-(2-carboxyethoxymethyl)-propoxy]propanoic acid 
• 1229609-36-2 C₅₇H₁₀₄N₁₀O₁₄ 
• 1314357-59-9 C₁₂₀H₁₈₅N₁₉O₃₅S₃ 
• 200133-17-1 benzyl N-tris[2-{[({tris[[2-(methoxycarbonyl)ethoxy]methyl]methyl}amino)carbonyl]ethoxy}methyl]methylcarbamate 

Relevant academic research and scientific papers

TARGETED PLASMA PROTEIN DEGRADATION

The present invention is directed to the bifunctional compounds and the use of such bifunctional compounds to lower plasma levels of extracellular target molecules by lysosomal degradation. Such bifunctional compounds have a cell surface receptor ligand covalently linked to a ligand that is capable of binding to an extracellular target molecule (such as a ligand for a growth factor, a cytokine, a chemokine, a hormone, a neurotransmitter, a capsid, a soluble receptor, an extracellular secreted protein, an antibody, a lipoprotein, an exosome, a virus, a cell, or a plasma membrane protein), where the cell surface receptor is associated with receptor mediated endocytosis, including asialoglycoprotein receptor (ASGPR) mediated lysosomal degradation and mannose-6-phosphate (M6PR) mediated lysosomal degradation. Pharmaceutical compositions comprising such bifunctional compounds and methods of treating a disease or disorder mediated by an extracellular molecule using such bifunctional compounds are also provided herein.

Assessing changes in the expression levels of cell surface proteins with a turn-on fluorescent molecular probe

Tri-nitrilotriacetic acid (NTA)-based fluorescent probes were developed and used to image His-tagged-labelled outer membrane protein C (His-OmpC) in liveEscherichia coli. One of these probes was designed to light up upon binding, which provided the means

Receptor-Specific Delivery of Peptide Nucleic Acids Conjugated to Three Sequentially Linked N-Acetyl Galactosamine Moieties into Hepatocytes

Peptide nucleic acids (PNAs) are DNA analogs that bind with high affinity to DNA and RNA in a sequence-specific manner but have poor cell permeability, limiting use as therapeutic agents. The work described here is motivated by recent reports of efficient gene silencing specifically in hepatocytes by small interfering RNAs conjugated to triantennary N-acetyl galactosamine (GalNAc), the ligand recognized by the asialoglycoprotein receptor (ASGPR). PNAs conjugated to either triantennary GalNAc at the N-terminus (the branched architecture) or monomeric GalNAc moieties anchored at Cγ of three consecutive PNA monomers of N-(2-aminoethyl)glycine (aeg) scaffolds (the sequential architecture) were synthesized on the solid phase. These formed duplexes with complementary DNA and RNA as shown by UV and circular dichroism spectroscopy. The fluorescently labeled analogs of GalNAc-conjugated PNAs were internalized by HepG2 cells that express the ASGPR but were not taken up by HEK-293 cells that lack this receptor. The sequential conjugate was internalized about 13-fold more efficiently than the branched conjugate into HepG2 cells, as demonstrated by confocal microscopy. The results presented here highlight the potential significance of the architecture of GalNAc conjugation for efficient uptake by target liver cells and indicate that GalNAc-conjugated PNAs have possible therapeutic applications.

GALNAC DERIVATIVES

Modified oligonucleotides comprising a GalNAc moiety of the present disclosure along with methods of making and use, e.g., against HBV are disclosed.

LIGAND-MODIFIED DOUBLE-STRANDED NUCLEIC ACIDS

The invention provides for double stranded nucleic acid molecules comprising a 5 'extension of the sense or antisense strand and further comprising a plurality of nucleotides that are conjugated to a ligand and methods of using the double-stranded nucleic acid molecules. Ligand-modified oligomers where the sense stands form a tetraloop provide new potent and stable RNA interference agents. These dsNA molecules are synthesized using a plurality of nucleotides that include ligand-modified monomers, nucleotide analog monomers, modified nucleotide monomers and the like, using standard nucleotide synthetic methods and systems.

MONONUCLEOTIDES HAVING A BIOREVERSIBLE DISULFIDE GROUP

The invention features a mononucleotide comprising a nucleobase bonded to a sugar having a 3'-carbon and a 5'-carbon, where the 5'-carbon is bonded to a phosphorus (V) atom of a phosphate group through an oxygen atom, the phosphorus (V) atom being bonded to (i) a disulfide bioreversible group through an oxygen atom; and (ii) (a) optionally substituted amino, optionally substituted alkoxy, optionally substituted aryloxy, or optionally substituted heteroaryloxy; or (b) the 3'-carbon through an oxygen atom. The invention also features methods of delivering the mononucleotide to a cell and methods of treating a subject having Hepatitis C.

TARGETED THERAPEUTIC NUCLEOSIDES AND THEIR USE

Provided herein are compounds comprising one or more therapeutic nucleosides and one or more targeting groups. In certain embodiments, the compounds further comprise one or more oligonucleotides. In certain embodiments, a targeting group comprises one or more N-Acetylgalactosamine.

COMPOSITIONS AND METHODS FOR ENHANCED INTESTINAL ABSORPTION OF CONJUGATED OLIGOMERIC COMPOUNDS

Provided herein are compositions and methods for non-parenteral delivery of conjugated oligomeric compounds. In certain embodiments, compositions and methods are provided for oral delivery of conjugated oligomeric compounds. In certain embodiments, the ol

COMPOSITIONS AND METHODS FOR MODULATING COMPLEMENT FACTOR B EXPRESSION

The present embodiments provide methods, compounds, and compositions for treating, preventing, or ameliorating a disease associated with dysregulation of the complement alternative pathway by administering a Complement Factor B (CFB) specific inhibitor to a subject.

COMPOSITIONS AND METHODS FOR MODULATING GROWTH HORMONE RECEPTOR EXPRESSION

The present embodiments provide methods, compounds, and compositions for treating, preventing, ameliorating a disease associated with excess growth hormone using antisense compounds oligonucleotides targeted to growth hormone receptor (GHR).