67673-39-6

Upstream product

• 67817-30-5 1,3,4,6-tetra-O-acetyl-2-azido-2-deoxy-alpha-D-galactopyranose 
• 1772-03-8 D-(+)-galactosamine hydrochloride 
• 68733-26-6 2-deoxy-2-azidogalactopyranose 
• 10257-28-0 D-Galactose 
• 3068-32-4 1-bromo-2,3,4,6-tetra-O-acetyl-D-galactopyranose 
• 25878-60-8 D-galactose pentaacetate 
• 68733-05-1 peracetylated α-glycosyl nitrate 2-azido-2-deoxy-D-galactopyranose 
• 75-09-2 dichloromethane 
• 71-91-0 tetraethylammonium bromide 
• 4163-60-4 β-D-galactose peracetate 
• 3068-32-4 1-bromo-1-deoxy-2,3,4,6-tetra-O-acetyl-a-D-galactopyranoside 
• 197158-78-4 1,2,3,4,6-penta-O-acetyl-D-galactopyranose 
• 4098-06-0 triacetyl-D-galactal 
• 196398-25-1 3,4,6-tri-O-acetyl-2-azido-2-deoxy-α/β-D-galactopyranosyl nitrate 

Downstream Products

• 110101-20-7 benzyl O-(3,4,6-tri-O-acetyl-2-azido-2-deoxy-β-D-galactopyranosyl)-(1-3)-O-(2,6-di-O-benzyl-β-D-galactopyranosyl)-(1-3)-2-azido-4,6-di-O-benzyl-2-deoxy-β-D-galactopyranoside 
• 101973-58-4 benzyl O-(3,4,6-tri-O-acetyl-2-azido-2-deoxy-β-D-galactopyranosyl)-(1-4)-O-(2,6-di-O-benzyl-β-D-galactopyranosyl)-(1-3)-2-azido-4,6-di-O-benzyl-2-deoxy-β-D-galactopyranoside 
• 97604-42-7 benzyl 2-azido-2-deoxy-β-D-galactopyranoside 
• 162105-02-4 ethyl 3,4-di-O-acetyl-2-benzyloxycarbonylamino-2-deoxy-6-O-(3',4',6'-tri-O-acetyl-2'-azido-2'-deoxy-α-D-galactopyranosyl)-α-D-glucopyranoside 
• 141462-11-5 N^α-(9H-fluoren-9-yl)methoxycarbonyl-O-(3,4,6-tri-O-acetyl-2-azido-2-deoxy-α-D-galactopyranosyl)-L-serine pentafluorophenyl ester 
• 172325-03-0 N-diphenylmethylene-O-(3,4,6-tri-O-acetyl-2-azido-2-deoxy-α-D-galactopyranosyl)-L-serine benzyl ester 
• 172325-06-3 N-diphenylmethylene-O-(3,4,6-tri-O-acetyl-2-azido-2-deoxy-α-D-galactopyranosyl)-L-threonine diphenylmethyl ester 
• 125760-22-7 p-methylphenyl 2-deoxy-2-azido-1-thio-β-D-galactopyranoside 
• 211869-87-3 Acetic acid (2R,3R,4R,5R,6S)-3-acetoxy-2-acetoxymethyl-5-azido-6-[(2R,3R,4S,5R,6R)-5-benzyloxy-2-benzyloxymethyl-4-hydroxy-6-(2-trimethylsilanyl-ethoxy)-tetrahydro-pyran-3-yloxy]-tetrahydro-pyran-4-yl 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

Enhanced Binding and Reduced Immunogenicity of Glycoconjugates Prepared via Solid-State Photoactivation of Aliphatic Diazirine Carbohydrates

Biological conjugation is an important tool employed for many basic research and clinical applications. While useful, common methods of biological conjugation suffer from a variety of limitations, such as (a) requiring the presence of specific surface-exposed residues, such as lysines or cysteines, (b) reducing protein activity, and/or (c) reducing protein stability and solubility. Use of photoreactive moieties including diazirines, azides, and benzophenones provide an alternative, mild approach to conjugation. Upon irradiation with UV and visible light, these functionalities generate highly reactive carbenes, nitrenes, and radical intermediates. Many of these will couple to proteins in a non-amino-acid-specific manner. The main hurdle for photoactivated biological conjugation is very low yield. In this study, we developed a solid-state method to increase conjugation efficiency of diazirine-containing carbohydrates to proteins. Using this methodology, we produced multivalent carbohydrate-protein conjugates with unaltered protein charge and secondary structure. Compared to carbohydrate conjugates prepared with amide linkages to lysine residues using standard NHS conjugation, the photoreactive prepared conjugates displayed up to 100-fold improved binding to lectins and diminished immunogenicity in mice. These results indicate that photoreactive bioconjugation could be especially useful for in vivo applications, such as lectin targeting, where high binding affinity and low immunogenicity are desired.

IN VIVO ASSEMBLY OF ASGPR BINDING THERAPEUTICS

Compounds are provided that assemble together in vivo to form an ASGPR-binding compound that has an asialoglycoprotein receptor (ASGPR) binding ligand bound to an extracellular protein binding ligand for the selective degradation of the target extracellular protein in vivo to treat disorders mediated by the extracellular protein.

ASGPR-BINDING COMPOUNDS FOR THE DEGRADATION OF EXTRACELLULAR PROTEINS

Compounds and compositions that have an asialoglycoprotein receptor (ASGPR) binding ligand bound to an extracellular protein binding ligand for the selective degradation of the target extracellular protein in vivo to treat disorders mediated by the extracellular protein are described.

Synthesis and evaluation of sensitive coumarin-based fluorogenic substrates for discovery of α-N-acetyl galactosaminidases through droplet-based screening

As part of a search for a substrate for droplet-based microfluidic screening assay of α-N-acetylgalactosaminidases, spectral and physical characteristics of a series of coumarin derivatives were measured. From among these a new coumarin-based fluorophore, Jericho Blue, was selected as having optimal characteristics for our screen. A reliable method for the challenging synthesis of coumarin glycosides of α-GalNAc was then developed and demonstrated with nine examples. The α-GalNAc glycoside of Jericho Blue prepared in this way was shown to function well under screening conditions.

Total Synthesis of the Congested, Bisphosphorylated Morganella morganii Zwitterionic Trisaccharide Repeating Unit

Zwitterionic polysaccharides (ZPSs) activate T-cell-dependent immune responses by major histocompatibility complex class II presentation. Herein, we report the first synthesis of a Morganella morganii ZPS repeating unit as an enabling tool in the synthesis of novel ZPS materials. The repeating unit incorporates a 1,2-cis-α-glycosidic bond; the problematic 1,2-trans-galactosidic bond, Gal-β-(1 → 3)-GalNAc; and phosphoglycerol and phosphocholine residues which have not been previously observed together as functional groups on the same oligosaccharide. The successful third-generation approach leverages a first in class glycosylation of a phosphoglycerol-functionalized acceptor. To install the phosphocholine unit, a highly effective phosphocholine donor was synthesized.

Synthetic MUC1 antitumor vaccine with incorporated 2,3-sialyl-T carbohydrate antigen inducing strong immune responses with isotype specificity

The endothelial glycoprotein MUC1 is known to underlie alterations in cancer by means of aberrant glycosylation accompanied by changes in morphology. The heavily shortened glycans induce a collapse of the peptide backbone and enable accessibility of the latter to immune cells, rendering it a tumor-associated antigen. Synthetic vaccines based on MUC1 tandem repeat motifs, comprising tumor-associated 2,3-sialyl-T antigen, conjugated to the immunostimulating tetanus toxoid, are reported herein. Immunization with these vaccines in a simple water/oil emulsion produced a strong immune response in mice to which stimulation with complete Freund’s adjuvant (CFA) was not superior. In both cases, high levels of IgG1 and IgG2a/b were induced in C57BL/6 mice. Additional glycosylation in the immunodominant PDTRP domain led to improved binding of the induced antisera to MCF-7 breast tumor cells, compared with that of the monoglycosylated peptide vaccine.

Mucin architecture behind the immune response: Design, evaluation and conformational analysis of an antitumor vaccine derived from an unnatural MUC1 fragment

A tripartite cancer vaccine candidate, containing a quaternary amino acid (α-methylserine) in the most immunogenic domain of MUC1, has been synthesized and examined for antigenic properties in transgenic mice. The vaccine which is glycosylated with GalNAc at the unnatural amino acid, was capable of eliciting potent antibody responses recognizing both glycosylated and unglycosylated tumour-associated MUC1 peptides and native MUC1 antigen present on cancer cells. The peptide backbone of the novel vaccine presents the bioactive conformation in solution and is more resistant to enzymatic degradation than the natural counter part. In spite of these features, the immune response elicited by the unnatural vaccine was not improved compared to a vaccine candidate containing natural threonine. These observations were rationalized by conformational studies, indicating that the presentation and dynamics of the sugar moiety displayed by the MUC1 derivative play a critical role in immune recognition. It is clear that engineered MUC1-based vaccines bearing unnatural amino acids have to be able to emulate the conformational properties of the glycosidic linkage between the GalNAc and the threonine residues. The results described here will be helpful to the rational design of efficacious cancer vaccines.

Synthesis of tumor-associated MUC1-glycopeptides and their multivalent presentation by functionalized gold colloids

The mucin MUC1 is a glycoprotein involved in fundamental biological processes, which can be found over-expressed and with a distinctly altered glycan pattern on epithelial tumor cells; thus it is a promising target structure in the quest for effective carbohydrate-based cancer vaccines and immunotherapeutics. Natural glycopeptide antigens indicate only a low immunogenicity and a T-cell independent immune response; however, this major drawback can be overcome by coupling of glycopeptide antigens multivalently to immunostimulating carrier platforms. In particular, gold nanoparticles are well suited as templates for the multivalent presentation of glycopeptide antigens, due to their remarkably high surface-to-volume ratio in combination with their high biostability. In this work the synthesis of novel MUC1-glycopeptide antigens and their coupling to gold nanoparticles of different sizes are presented. In addition, the development of a new dot-blot immunoassay to test the potential antigen-antibody binding is introduced.

Synthesis of Tn/T antigen MUC1 glycopeptide BSA conjugates and their evaluation as vaccines

The tumor-associated mucin MUC1 over-expressed in most epithelial tumor tissues is considered a promising target for immunotherapy. The extracellular part of MUC1 contains a domain of numerous tandem repeats of the amino acid sequence HGVTSAPDTRPAPGSTAPPA, including five potential O-glycosylation sites. In this study, T9 and S15 have been chosen as the positions of glycosylation. The glycopeptides N-terminally equipped with a triethylene glycol spacer were synthesized by microwave-assisted Fmoc solid-phase peptide synthesis. After detachment from the resin and deprotection, the MUC1 glycopeptides were conjugated to bovine serum albumin (BSA). To evaluate the immunological properties, balb/c mice were immunized with these BSA vaccines. Copyright

Functional and structural characterization of drosocin and its derivatives linked O-GalNAc at Thr11 residue

Antimicrobial peptides have recently gained the much attention because of their ability to make defense system from attacking bacterial infections. Drosocin has been considered as very attractive antibiotic agents because of low toxicity against human erythrocytes and active at the low concentration. We have studied the structureactivity relationship of a glycopeptide drosocin focused on the N-acetyl-D-galactoside at Thr11 residue. Based on the radial diffusion assay, we found that the acetylation of carbohydrate moiety increased the antimicrobial activity and the Pro10, present in the middle of drosocin plays an important role in the antimicrobial activity. Our results provide a good lead compound for further studies on the design of drosocin-based analogues targeting glyco linked Thr site.