258351-86-9

Upstream product

• 98045-03-5 α-methyl N-(tert-butoxycarbonyl)aspartate 
• 30925-18-9 2-tert-butoxycarbonylamino-succinic acid 1-benzyl ester 
• 543-27-1 isobutyl chloroformate 
• 672-15-1 L-homoserine 
• 24424-99-5 di-tert-butyl dicarbonate 
• 210772-73-9 (S)-4-hydroxy-2-aminobutyric acid methyl ester 
• 41088-86-2 L-2-(tert-butyloxycarbonylamino)-4-hydroxybutyric acid 
• 77-78-1 dimethyl sulfate 
• 89985-91-1 tert-butyl pyridin-2-yl carbonate 
• 74-88-4 methyl iodide 
• 219870-51-6 methyl (2R)-2-[(tert-butoxy)carbonylamino]-5-methyl-5-phenyl-5-silahexanoate 
• 1620659-20-2 C₅H₁₁NO₃ 
• 745011-75-0 (R)-2-((tert-butoxycarbonyl)amino)-4-hydroxybutanoic acid 
• 38308-92-8 2-(tert-butoxycarbonylamino)-4-hydroxy-butanoic acid 

Downstream Products

• 76969-87-4 methyl (2S)-4-bromo-2-[(tert-butoxycarbonyl)amino]butanoate 
• 359781-97-8 methyl 4-azido-2S-{[(1,1-dimethylethoxy)carbonyl]amino}butyrate 
• 87884-15-9 9--6-cyano-5,6,7,8,9-pentadeoxy-2,3-O-isopropylidene-β-D-ribo-deca-6-enofuranosyluronate>-adenine 
• 101650-14-0 methyl (2S)-2-(tert-butoxycarbonyl)amino-4-iodobutanoate 
• 120042-09-3 methyl N-(tert-butoxycarbonyl)-O-tosyl-L-homoserinate 
• 219752-75-7 methyl (2R)-<(tert-butyloxycarbonyl)amino>-4-iodobutyrate 
• 168077-38-1 N-tert-butyloxycarbonyl-α-amino-γ-bromobutyric acid methyl ester 
• 500720-15-0 4-tert-Butoxycarbonylamino-[1,2]Oxazinan-3-one 
• 132872-26-5 2-(tert-butoxycarbonylamino)-γ-butyrolactol 

Relevant academic research and scientific papers

Perfluoro-tert-butyl Homoserine Is a Helix-Promoting, Highly Fluorinated, NMR-Sensitive Aliphatic Amino Acid: Detection of the Estrogen Receptor·Coactivator Protein-Protein Interaction by 19F NMR

Highly fluorinated amino acids can stabilize proteins and complexes with proteins, via enhanced hydrophobicity, and provide novel methods for identification of specific molecular events in complex solutions, via selective detection by 19F NMR and the absence of native 19F signals in biological contexts. However, the potential applications of 19F NMR in probing biological processes are limited both by the strong propensities of most highly fluorinated amino acids for the extended conformation and by the relatively modest sensitivity of NMR spectroscopy, which typically constrains measurements to mid-micromolar concentrations. Herein, we demonstrate that perfluoro-tert-butyl homoserine exhibits a propensity for compact conformations, including α-helix and polyproline helix (PPII), that is similar to that of methionine. Perfluoro-tert-butyl homoserine has nine equivalent fluorines that do not couple to any other nuclei, resulting in a sharp singlet that can be sensitively detected rapidly at low micromolar concentrations. Perfluoro-tert-butyl homoserine was incorporated at sites of leucine residues within the α-helical LXXLL short linear motif of estrogen receptor (ER) coactivator peptides. A peptide containing perfluoro-tert-butyl homoserine at position i + 3 of the ER coactivator LXXLL motif exhibited a Kd of 2.2 μM for the estradiol-bound estrogen receptor, similar to that of the native ligand. 19F NMR spectroscopy demonstrated the sensitive detection (5 μM concentration, 128 scans) of binding of the peptide to the ER and of inhibition of protein-protein interaction by the native ligand or by the ER antagonist tamoxifen. These results suggest diverse potential applications of perfluoro-tert-butyl homoserine in probing protein function and protein-protein interfaces in complex solutions.

Synthesis and Biological Evaluation of CF3Se-Substituted α-Amino Acid Derivatives

Several CF3Se-substituted α-amino acid derivatives, such as (R)-2-amino-3-((trifluoromethyl)selanyl)propanoates (5 a/6 a), (S)-2-amino-4-((trifluoromethyl)selanyl)butanoates (5 b/6 b), (2R,3R)-2-amino-3-((trifluoromethyl)selanyl)butanoates (5 c/6 c), (R)-2-((S)-2-amino-3-phenylpropanamido)-3-((trifluoromethyl)selanyl)propanoates (11 a/12 a), and (R)-2-(2-aminoacetamido)-3-((trifluoromethyl)selanyl)propanoates (11 b/12 b), were readily synthesized from natural amino acids and [Me4N][SeCF3]. The primary in vitro cytotoxicity assays revealed that compounds 6 a, 11 a and 12 a were more effective cell growth inhibitors than the other tested CF3Se-substituted derivatives towards MCF-7, HCT116, and SK-OV-3 cells, with their IC50 values being less than 10 μM for MCF-7 and HCT116 cells. This study indicated the potentials of CF3Se moiety as a pharmaceutically relevant group in the design and synthesis of novel biologically active molecules.

Synthesis and delivery of a stable phosphorylated ubiquitin probe to study ubiquitin conjugation in mitophagy

Protein post-translational modifications are involved in essentially all aspects of cellular signaling. Their dynamic nature and the difficulties in installing them using enzymatic approaches limits their direct study in human cells. Reported herein is the first synthesis, delivery and cellular study of a stable phosphoubiquitin probe. Our results compare Parkin's substrate preference during mitophagyviadirect visualization of a phosphorylated ubiquitin probe in the cellular environment.

Easy Production of “Difficult Peptides” Using Cell-Free Protein Synthesis and a New Methionine Analogue as a Latent Peptide Cleavage Site

Aliphatic γ-chloro-α-amino acids incorporated in place of their canonical analogues through cell-free protein synthesis act as heat-labile linkers, offering a useful strategy for the straightforward production of target peptides as fusion proteins, from which the targets are readily released. Until now, the natural abundance of aliphatic amino acids in peptides has limited the scope of the method, as it leads to undesired cleavage sites in synthesized products, but here the authors report the development of a new cleavable chloro amino acid that incorporates in place of the relatively rare amino acid methionine, thus greatly expanding the scope of producible targets. This new strategy is employed for simplified peptide synthesis with a methionine-free fusion partner, allowing single-site incorporation of the cleavable linker for clean release and easy purification of the target peptide. Its utility is demonstrated through the straightforward preparation of two peptides reported to be challenging targets and not accessible through standard solid-phase chemical methodologies, as well as analogues.

NOVEL HISTONE METHYLTRANSFERASE INHIBITORS

The present invention relates to novel compounds of formula (I) as defined herein. The compounds are inhibitors of histone methyltransferases of the seven-beta-strand family, in particular of KMT9.

Rhodium(I) and Iridium(I) N-Heterocyclic carbene complexes of imidazolium functionalized amino acids and peptides

The conjugation of organometallic complexes to peptides is generally achieved through covalent organic linkages of the metal's ligand to the peptide. Examples of direct coordination to metal centers by amino acid side chain residues remain rare. In one such example, side chain methylation of the natural amino acid histidine (His) resulted in an imidazolium functionalized amino acid which was used for the synthesis of rhodium(I), iridium(I), iridium(III), palladium(II) and ruthenium(III) N-heterocyclic carbene (NHC) complexes of the single amino acid and peptides containing this amino acid. Here, we have synthesized two new, non-natural imidazolium functionalized amino acid derivatives, which were used for solid phase peptide synthesis and for the synthesis of [M(COD)(NHC)Cl] (COD = 1,5 cyclooctadiene) complexes of Rh(I) and Ir(I). In total, six new complexes of the single amino acids and four complexes where the amino acids are present in a peptide environment were synthesized. Their characterization provides convincing evidence of conversion of the imidazolium moiety to an NHC ligand and thus the presence of a direct metal-carbon bond between the metal center and the amino acid side chain. Therefore, our compounds represent unique examples of peptide-conjugated complexes that bear the potential to be used for the synthesis of N-heterocyclic carbene complexes conjugated to cancer cell targeting peptides.

Trifluoromethyl selenoamino acid derivative and preparation method thereof

The invention discloses a trifluoromethyl selenoamino acid derivative and a preparation method thereof. The preparation method comprises the following steps: by taking amino acid as an initial raw material, performing an N-Boc protection reaction with an N-Boc protection reagent so as to obtain amino N-Boc protected amino acid; performing an esterification reaction on the amino N-Boc protected amino acid with an esterification reagent so as to obtain an esterification product; performing a sulfonylation reaction on the esterification product with a sulfonylation reagent so as to obtain a sulfonylation product; and performing a trifluoromethyl selenium formation reaction on the sulfonylation product with a trifluoromethyl selenium salt, so as to obtain the amino N-Boc protected trifluoromethyl selenoamino acid derivative. The reaction is not only simple and convenient in operation, mild in condition, high in yield and good in functional group resistance, but also cheap in raw material,easy in raw material obtaining, and a very practical method is provided for synthesizing the trifluoromethyl selenoamino acid derivative.

HETEROCYCLIC COMPOUNDS AS PRMT5 INHIBITORS

The compounds of Formula I, Formula Ia, and Formula Ib are described herein along with their analogs, tautomeric forms, stereoisomers, polymorphs, hydrates, solvates, pharmaceutically acceptable salts, pharmaceutical compositions, metabolites, and prodrugs thereof. These compounds inhibit PRMT5 and are useful as therpeautic or ameliorating agent for diseases that are involved in cellular growth such as malignant tumors, schizophrenia, Alzheimer's disease, Parkinson's disease and the like.

POLYMYXIN ANALOGS USEFUL AS ANTIBIOTIC POTENTIATORS

The disclosure provides compounds of the formula (I) or a tautomer thereof, or a pharmaceutically acceptable salt of either of the foregoing. The variables A, R1, and R2 are defined in the disclosure. The disclosure further includes pharmaceutical compositions comprising a compound of formula I together with at least one pharmaceutically acceptable carrier. The disclosure also includes a method of sensitizing bacteria to an antibacterial agent, comprising administering to a patient infected with the bacteria, simultaneously or sequentially, a therapeutically effective amount of the antibacterial agent and a compound of formula (I).

CALPAIN MODULATORS AND METHODS OF PRODUCTION AND USE THEREOF

The present technology relates to compounds, kits, compositions, and methods useful for the treatment of fibrotic disease. In some aspects, the present technology provides for treatment of various diseases or disorders associated or mediated, at least in part, by calpains, such as CAPN1, CAPN2, and/or CAPN9. The present technology is generally applicable to compounds which inhibit myofibroblast differentiation.