83306-52-9

Upstream product

• 108-30-5 succinic acid anhydride 
• 41355-50-4 2,3,4,6-tetra-O-acetyl-β-D-galactopyranosylamine 
• 3068-32-4 1-bromo-1-deoxy-2,3,4,6-tetra-O-acetyl-a-D-galactopyranoside 
• 13992-26-2 (2R,3S,4S,5R,6R)-2-(acetoxymethyl)-6-azidotetrahydro-2H-pyran-3,4,5-triyl triacetate 
• 3068-32-4 1-bromo-2,3,4,6-tetra-O-acetyl-D-galactopyranose 
• 83306-50-7 N-(β-D-galactopyranosyl)-3-methoxycarbonylpropanamide 
• 6318-23-6 1-amino-1-deoxy-β-D-galactose 
• 4163-60-4 β-D-galactose peracetate 
• 108-24-7 acetic anhydride 
• 27010-46-4 N-((2R,3R,4S,5R,6R)-3,4,5-Trihydroxy-6-hydroxymethyl-tetrahydro-pyran-2-yl)-succinamic acid 

Relevant academic research and scientific papers

Synthesis of glycolipopeptidic building blocks for carbohydrate receptor discovery

A class of glycolipopeptides for use as building blocks for a new type of dynamic combinatorial library is reported. The members of the library consist of a variable carbohydrate moiety, coded amino acids, and lipoamino acids in order to convert them into amphiphiles. Glycolipopeptidic amphiphiles interact through non-covalent bonding when mixed together in aqueous phase and form micelles in dynamic close-packed fluid mosaic arrays. The head groups of amphiphiles are exposed on the micelle surface, providing entities which could be screened in biological assays to find the most potent combination of building blocks in order to identify new bioactive carbohydrate ligands.

Synthesis of divalent ligands of β-thio- And β-N-galactopyranosides and related lactosides and their evaluation as substrates and inhibitors of Trypanosoma cruzi trans-sialidase

In this work we describe the synthesis of mono- and divalent β-N - and β-S-galactopyranosides and related lactosides built on sugar scaffolds and their evaluation as substrates and inhibitors of the Trypanosoma cruzi trans-sialidase (TcTS). This enzyme catalyzes the transfer of sialic acid from an oligosaccharidic donor in the host, to parasite βGalp terminal units and it has been demonstrated that it plays an important role in the infection. Herein, the enzyme was also tested as a tool for the chemoenzymatic synthesis of sialic acid containing glycoclusters. The transfer reaction of sialic acid was performed using a recombinant TcTS and 3'-sialyllactose as sialic acid donor, in the presence of the acceptor having βGalp non reducing ends. The products were analyzed by high performance anion exchange chromatography with pulse amperometric detection (HPAEC-PAD). The ability of the different S-linked and N-linked glycosides to inhibit the sialic acid transfer reaction from 3'-sialyllactose to the natural substrate N-acetyllactosamine, was also studied. Most of the substrates behaved as good acceptors and moderate competitive inhibitors. A di-N -lactoside showed to be the strongest competitive inhibitor among the compounds tested (70% inhibition at equimolar concentration). The usefulness of the enzymatic trans-sialylation for the preparation of sialylated ligands was assessed by performing a preparative sialylation of a divalent substrate, which afforded the monosialylated compound as main product, together with the disialylated glycocluster.

PCSK9 ANTAGONIST COMPOUNDS

Disclosed are compounds of Formula I, or a salt thereof: where A, B, D, X, R1, R2 and R8 are as defined herein, which compounds have properties for antagonizing PCSK9. Also described are pharmaceutical formulations comprising the compounds of Formula I or their salts, and methods of treating cardiovascular disease and conditions related to PCSK9 activity, e.g. atherosclerosis, hypercholesterolemia, coronary heart disease, metabolic syndrome, acute coronary syndrome, or related cardiovascular disease and cardiometabolic conditions.

α1,4-Galactosyltransferase-catalyzed glycosylation of sugar and lipid modified Leu-enkephalins

Glycosylation of therapeutic peptides has been reported to improve delivery and targeting of various vaccines and drugs to specific cells/tissues. However, chemical synthesis of complex oligosaccharide derivatives via conventional methods can be challengi

Development of carbohydrate-based scaffolds for restricted presentation of recognition groups. Extension to divalent ligands and implications for the structure of dimerized receptors

The solution structure of glycosyl amides has been studied by using NMR. A strong preference is displayed by tertiary aromatic glycosyl amides for E-anti structures in contrast with secondary aromatic glycosyl amides where Z-anti structures predominate. The structural diversity displayed by these classes of molecules would seem to be important as the directional properties of the aromatic ring, or groups attached to the aromatic ring, would be determined by choosing to have either a secondary or tertiary amide at the anomeric center and could be considered when designing bioactive molecules with carbohydrate scaffolds. The structural analysis was also carried out for related divalent secondary and tertiary glycosyl amides and these compounds display preferences similar to that of the monovalent compounds. The constrained divalent compounds have potential for promoting formation of clusters that will have restricted structure and thus have potential for novel studies of mechanisms of action of multivalent ligands. Possible applications of such compounds would be as scaffolds for the design and synthesis of ligands that will facilitate protein - protein or other receptor - receptor interactions. The affinity of restricted divalent (or higher order) ligands, designed to bind to proteins that recognize carbohydrates which would facilitate clustering and concomitantly promote protein - protein interactions, may be significantly higher than monovalent counterparts or multivalent ligands without these properties. This may be useful as a new approach in the development of therapeutics based on carbohydrates.

Application of Ugi reactions in synthesis of divalent neoglycoconjugates: Evidence that the sugars are presented in restricted conformation

(Equation presented) The Ugi reaction has been used to prepare divalent galactose derivatives. NMR analysis shows that a divalent neoglycoconjugate, where the glycopeptides are bridged by a terephthaloyl group, is an 83:17 mixture of two conformers; the amide groups of the major isomer have E-anti conformations. The spatial relationship and the relative orientation of the sugars are restricted, which may have consequences for the recognition of this and related structures in biological systems.

Synthesis of some N- and S-glycosides of D-galactose bearing hydrazinocarbonyl and diazomethylcarbonyl functions in the aglycon

We describe the synthesis of N- and S-glycosides derived from D-galactopyranose in which the aglycon bears certain reactive groups.In a first series, the anomeric carbon is linked to an amino group that is acylated by a functionalized succinic acid chain.The terminal group of the aglycon moiety is a hydrazide function which can be converted by ultraviolet light irradiation into an azide and a nitrene.Altenatively, the terminal group is a diazoketone function which can be converted into a carbene, by ultraviolet light irradiation.A second series comprises glycosides of 1-thio-β-D-galactopyranose.The aglycon consists of a 6-carbon chain with a carboxylic end group.The latter has been converted into a hydrazide and diazoketone function.We show that the diazo group of the diazoketones (compounds 5 and 12) is susceptible to decomposition by ultraviolet irradiation, being nearly quantitatively decomposed after 3 minutes.These compounds add to a growing list of hexose derivatives which can be used in the field of photoaffinity-labeling of the sugar binding sites of certain lectins and of hexose transport systems, or to prepare modified proteins or ligands for affinity chromatography.