118358-66-0

Upstream product

• 1738-72-3 L-serine benzyl ester 
• 82911-69-1 N-(9H-fluoren-2-ylmethoxycarbonyloxy)succinimide 
• 60022-62-0 L-serine benzyl ester hydrochloride 
• 28920-43-6 (fluorenylmethoxy)carbonyl chloride 
• 73724-45-5 N-(9H-fluoren-9-ylmethoxycarbonyl)-L-serine 
• 100-51-6 benzyl alcohol 
• 100-39-0 benzyl bromide 
• 73724-45-5 (R)-N-(fluoren-9-ylmethoxycarbonyl)serine 
• 212688-51-2 Fmoc-D-Ser(Trt)-OH 
• 866832-84-0 N-(9H-fluoren-9-ylmethoxycarbonyl)-O-trityl-D-serine benzyl ester 
• 558-43-0 2-Methyl-1,2-propanediol 
• 171820-92-1 N-9-fluorenylmethoxycarbonyl-O-trityl-L-serine benzyl ester 

Downstream Products

• 84010-48-0 benzyl-N-(fluorenylmethyloxycarbonyl)-O-(2,3,4,6-tetra-O-benzoyl β-D-glucopyranosyl) L-serinate 
• 118358-94-4 3-O-(2,3,4-Tri-O-acetyl-β-D-xylopyranosyl)-N-(fluorenylmethoxycarbonyl)-L-serin-benzylester 
• 109977-95-9 Fmoc-Ser(3,4,6-Tri-O-acetyl-2-desoxy-2-iod-α-D-mannopyranosyl)-OBzl 
• 109978-00-9 Fmoc-Ser(3,4,6-Tri-O-acetyl-2-desoxy-2-iod-α-D-talopyranosyl)-OBzl 
• 84010-49-1 C₅₁H₄₃NO₁₂ 
• 118358-79-5 N-Fmoc-O-(2,3,4,6-tetra-O-acetyl-α-D-mannopyranosyl)-L-serine benzyl ester 
• 118358-37-5 N-9-fluorenylmethoxycarbonyl-O-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-L-serine benzyl ester 
• 213331-74-9 (S)-3-((3aR,4R,6S,7R,7aR)-7-Azido-2,2-dimethyl-4-triisopropylsilanyloxymethyl-tetrahydro-[1,3]dioxolo[4,5-c]pyran-6-yloxy)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-propionic acid benzyl ester 
• 100929-00-8 benzyl O-(3,4,6-tri-O-acetyl-2-azido-2-deoxy-α-D-galactopyranosyl)-N-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-serinate 

Relevant academic research and scientific papers

Fluorescence-based detection of single nucleotide permutation in DNA via catalytically templated reaction

Templated reduction of low fluorescence azidocoumarin-PNA conjugate to high fluorescence aminocoumarin was achieved using a catalytic amount of DNA with single nucleotide resolution. The Royal Society of Chemistry.

O-SUBSTITUTED SERINE DERIVATIVE PRODUCTION METHOD

It was discovered that a cyclic sulfamidate can be produced by reacting an amino acid derivative with a cyclization reagent. In addition, it was discovered that an O-substituted serine derivative can be produced by reacting a cyclic sulfamidate with an alcohol.

In vitro synthesis of mucin-type O-glycans using saccharide primers comprising GalNAc-Ser and GalNAc-Thr residues

Mucin-type O-glycosylation of serine or threonine residue in proteins is known to be one of the major post-translational modifications. In this study, two novel alkyl glycosides, Nα-lauryl-O-(2-acetamido-2-deoxy-α-D-galactopyranosyl)-L-serineamide (GalNAc-Ser-C12) and Nα-lauryl-O-(2-acetamido-2-deoxy-α-D-galactopyranosyl)-L-threonineamide (GalNAc-Thr-C12) were synthesized as saccharide primers to prime mucin-type O-glycan biosynthesis in cells. Upon incubating human gastric cancer MKN45 cells with the saccharide primers, 22 glycosylated products were obtained, and their structures were analyzed using liquid chromatography-mass spectrometry and enzyme digestion. The amounts of glycosylated products were dependent on the amino acid residues in the saccharide primers. For example, in vitro synthesis of T antigen (Galβ1-3GalNAc), fucosyl-T (Fucα1-2Galβ1-3GalNAc), and sialyl-T (NeuAcα2-3Galβ1-3GalNAc) preferred a serine residue, whereas sialyl-Tn (NeuAcα2-6GalNAc) preferred a threonine residue. Furthermore, the glycosylated products derived from GalNAc-Ser/Thr-C12 and Gal-GalNAc-Ser/Thr-C12 using cell-free synthesis showed the same amino acid selectivity as those in the cell experiments. These results indicate that glycosyltransferases involved in the biosynthesis of mucin-type O-glycans distinguish amino acid residues conjugated to GalNAc. The saccharide primers developed in this study might be useful for comparing mucin-type oligosaccharides in cells and constructing oligosaccharide libraries to study cell function.

Progress toward the assembly of the bicyclic theonellamide skeleton

An orthogonally protected τ-histidinoalanine residue was synthesized via regioselective alkylation of optically pure Boc-L-His-OTCE (TCE = trichloroethyl) with a sulfamidate electrophile derived from Fmoc-D-Ser-OBn. The goal was the synthesis of a non-natural theonellamide, invoking readily accessible variants of the other 10 amino acids. Peptide fragments corresponding to the east and west rings of “theonellamide X″ were synthesized in solution. Each ring was formed independently, providing insights into protecting group limitations, side reactions, and the optimal order of events to approach the formation of the bicyclic system. Ultimately, an undecapeptide was prepared, with the eastern ring formed. The twelfth amino acid, an L-α-aminoadipic acid building block, was prepared and preliminary investigations into its attachment to the undecapeptide are reported.

Amino acid derivative

The invention provides a novel amino acid derivative. The derivative is applied to modify a polypeptide drug to achieve the purposes of resisting degradation of a proteolytic enzyme and prolonging thehalf-life period of the drugs. The invention provides two methods for preparing the amino acid derivative.

COMPOSITIONS AND METHODS OF TREATING CANCER AND INFECTIONS USING BACTERIOPHAGE AND ITS MUTANTS

Provided herein are vaccine composition comprising an antigen conjugated to a capsid, wherein the capsid comprises wild type or native sequence. Provided herein are also vaccine composition comprising an antigen conjugated to a capsid, wherein said capsid comprises at least one mutation, such as a non-natural mutation. Such compositions are useful in the treatment and prevention of pathogenic infections, inflammatory diseases, and neurodegenerative disease, and cancer, among others.

Solid-Phase Synthesis of the Aged-Nonapeptide-Nerve-Agent Adduct of Butyrylcholinesterase as Reference Materials for Analytical Verification

Two pathways were developed and investigated for the synthesis of the ‘aged’-nonapeptide nerve-agent bioadduct of human butyrylcholinesterase (BuChE). Considering the fast ageing of nerve-agent adducts of BuChE in patients and biomedical samples this target molecule is of paramount relevance for quantitative analysis with respect to the Chemical Weapons Convention. Two approaches using a precursor bearing a hydroxyl on its phosphonyl moiety and a benzyl protected precursor were considered. Several impurities were identified and circumvented during the optimization of the peptide synthesis step. The ‘aged’-nonapeptide adduct was successfully synthesized by solid-phase-peptide-synthesis (SPPS).

A Synthetic MUC1 Glycopeptide Bearing βGalNAc-Thr as a Tn Antigen Isomer Induces the Production of Antibodies against Tumor Cells

This study presents the synthesis of the novel protected O-glycosylated amino acid derivatives 1 and 2, containing βGalNAc-SerOBn and βGalNAc-ThrOBn units, respectively, as mimetics of the natural Tn antigen (αGalNAc-Ser/Thr), along with the solid-phase assembly of the glycopeptides NHAcSer-Ala-Pro-Asp-Thr[αGalNAc]-Arg-Pro-Ala-Pro-Gly-BSA (3-BSA) and NHAcSer-Ala-Pro-Asp-Thr[βGalNAc]-Arg-Pro-Ala-Pro-Gly-BSA (4-BSA), bearing αGalNAc-Thr or βGalNAc-Thr units, respectively, as mimetics of MUC1 tumor mucin glycoproteins. According to ELISA tests, immunizations of mice with βGalNAc-glycopeptide 4-BSA induced higher sera titers (1:320 000) than immunizations with αGalNAc-glycopeptide 3-BSA (1:40 000). Likewise, flow cytometry assays showed higher capacity of the obtained anti-glycopeptide 4-BSA antibodies to recognize MCF-7 tumor cells. Cross-recognition between immunopurified anti-βGalNAc antibodies and αGalNAc-glycopeptide and vice versa was also verified. Lastly, molecular dynamics simulations and surface plasmon resonance (SPR) showed that βGalNAc-glycopeptide 4 can interact with a model antitumor monoclonal antibody (SM3). Taken together, these data highlight the improved immunogenicity of the unnatural glycopeptide 4-BSA, bearing βGalNAc-Thr as Tn antigen isomer.

α-Selective glycosylation affords mucin-related GalNAc amino acids and diketopiperazines active on Trypanosoma cruzi

This work addresses the synthesis and biological evaluation of glycosyl diketopiperazines (DKPs) cyclo[Asp-(αGalNAc)Ser] 3 and cyclo[Asp-(αGalNAc)Thr] 4 for the development of novel anti-trypanosomal agents and Trypanosoma cruzi trans-sialidase (TcTS) inhibitors. The target compounds were synthetized by coupling reactions between glycosyl amino acids αGalNAc-Ser 7 or αGalNAc-Thr 8 and the amino acid (O-tBu)-Asp 17, followed by one-pot deprotection-cyclisation reaction in the presence of 20% piperidine in DMF. The protected glycosyl amino acid intermediates 7 and 8 were, in turn, obtained by α-selective, HgBr2-catalysed glycosylation reactions of Fmoc-Ser/Thr benzyl esters 12/14 with αGalN3Cl 11, being, subsequently, fully deprotected for comparative biological assays. The DKPs 3 and 4 showed relevant anti-trypanosomal effects (IC50 282-124 μM), whereas glycosyl amino acids 1 and 2 showed better TcTS inhibition (57-79%) than the corresponding DKPs (13-25%).

Influence of steric parameters on the synthesis of tetramates from α-amino-β-alkoxy-esters and Ph3PCCO

α-Aminoesters react with Ph3PCCO in a domino addition-Wittig cyclization sequence affording enantiomerically pure tetramates. In the case of β-oxo functionalized α-aminoesters, e.g., esters of serine, threonine or β-hydroxyornithine the yields of this reaction depend heavily on the bulkiness of the β-OR group and on the configuration of β-carbon atom C-3. Smaller residues and 2R/3R-configured aminoesters give better yields. The alkoxycarbonyl group of the ester moiety and the residue on the N-atom are less important. These findings can be accounted for by assuming an early puckered transition state for the intramolecular ring-closing Wittig reaction. The addition of sub-stoichiometric amounts of benzoic acid or N-hydroxysuccinimide (for acid-sensitive compounds) is advantageous in some cases as it accelerates the formation of the intermediate amide ylides.