We utilize the supramolecular self-assembling peptide of Nap-GDFDFDYDK to construct chemically programmed, self-assembling and self-adjuvant MUC1-based antitumor vaccines. The vaccines, with antigen and adjuvant conjugation through covalent bonds, elicited both humoral and cellular immune responses.

•Nine analogues from crude fondaparinux sodium were identified.•Their anticoagulant activity in vitro were tested.•The structure-activity relationships were confirmed.•The derivative Rrt1.17 was chemically synthesized.•Compared with fondaparinux, Rrt1.17 was a more efficient anticoagulant candidate.Fondaparinux, a synthetic pentasaccharide anticoagulant based on heparin antithrombin-binding domain, is derived from a chemical synthesis with more than 50 steps. Herein, we identified nine analogues separated from commercially available crude fondaparinux sodium, and tested their anticoagulant activity in vitro. Based on the activity results, the most active derivative Rrt1.17 was chemically synthesized. Biological properties in vitro and in vivo indicated that the well-defined derivative Rrt1.17 was a more efficient anticoagulant candidate compared with fondaparinux.

•A novel Hf(OTf)4-catalyzed Ferrier rearrangement.•Both mono- and disaccharide derived glycal as the substrates.•The efficient and stereoselectivity construction of 2,3-unsaturated O- and S-glycosides.A highly efficient method to afford 2,3-unsaturated glycosides was described. In the presence of Hafnium(IV) triflate, a variety of 2,3-unsaturated-O- and S-glycosides have been obtained by stereoselective glycosylation of 3,4,6-tri-O-acetyl-d-glucal and hexa-O-acetyl-d-lactal with various acceptors in good isolated yields.

D-Gluconhydroximo-1,5-lactam and its oxime-substituted derivatives were prepared and assessed for inhibition and pharmacological chaperone (PC) activities in Gaucher disease cell lines derived from N370S. The most active compound, O-(D-glucopyranosylidene) amino-Z-N-dodecylcarbamate (38), gave a nearly 2.0-fold increase in N370S β-GCase activity at 12.5 μM with no inhibition to other commercially available glucosidases. Docking studies of ligand–enzyme interactions have also been conducted to account for the results of enzyme activity increase. All these results demonstrate that compound 38 is a promising PC for the treatment of GD.

In this report, “armed and disarmed” theory was used to explain the selectivity of azide radical addition to glucals. We discovered that “armed” glucals were prone to undergo a kinetic process. The torsional strains govern the selectivity. Meanwhile, “disarmed” glucals preferred thermodynamic radical addition. We also applied our method to synthesize a sialic acid containing trisaccharide.

A simple and efficient method for the synthesis of pyranoid glycals utilizing the reductive elimination of glycopyranosyl bromides by zinc nanoparticles in an acetate buffer is described. A variety of pyranoid glycals derivatives were obtained, especially for the synthesis of 6-deoxy-4,6-O-benzylidene and disaccharide glycals with good yields.

An N-acetylhexosamine 1-kinase from Bifidobacterium infantis (NahK_15697), a guanosine 5′-diphosphate (GDP)-mannose pyrophosphorylase from Pyrococcus furiosus (PFManC), and an Escherichia coli inorganic pyrophosphatase (EcPpA) were used efficiently for a one-pot three-enzyme synthesis of GDP-mannose, GDP-glucose, their derivatives, and GDP-talose. This study represents the first facile and efficient enzymatic synthesis of GDP-sugars and derivatives starting from monosaccharides and derivatives.

An effective and stereo-controlled synthesis of 1,3,4-tris(benzyloxy)-2,5-diiodopentane starting from 2,3,5-tris(benzyloxy)pentane-1,4-diol was reported. Synthesis was improved to get the diiodide compound instead of forming the ring-closure product (benzyloxylated tetrahydrofuran). From the diiodide intermediate, the five-membered aza-sugar was synthesized with high yield.

Galactokinase (GalK), particularly GalK from Escherichia coli, has been widely employed for the synthesis of sugar-1-phosphates. In this study, a GalK from Bifidobacterium infantis ATCC 15697 (BiGalK) was cloned and over-expressed with a yield of over 80 mg/L cell cultures. The kcat/Km value of recombinant BiGalK toward galactose (164 s−1 mM−1) is 296 times higher than that of GalK from E. coli, indicating that BiGalK is much more efficient in the phosphorylation of galactose. The enzyme also exhibits activity toward galacturonic acid, which has never been observed on other wild type GalKs. Further activity assays showed that BiGalK has broad substrate specificity toward both sugars and phosphate donors. These features make BiGalK an attractive candidate for the large scale preparation of galactose-1-phosphate and derivatives.Graphical abstractHighlights► GalK from Bifidobacterium infantis was expressed over 80 mg/L cell cultures. ► The enzyme exhibits high activity toward galactose with a kcat/Km of 164 s−1 mM−1. ► The wild type enzyme could phosphorylate galacturonic acid. ► The enzyme utilizes a variety of nucleoside triphosphates as phosphate donors.

Protein O-GlcNAc glycosylation is a ubiquitous post-translational modification in metazoans. O-GlcNAcase (OGA), which is responsible for removing O-GlcNAc from serine or threonine residues, plays a key role in O-GlcNAc metabolism. Potent and selective O-GlcNAcase (OGA) inhibitors are useful tools for investigating the role of this modification in a broad range of cellular processes, and may also serve as drug candidates for treatment of neurodegenerative diseases. Biological screening of the gluco-configured tetrahydroimidazopyridine derivatives identified a compound as a potent and competitive inhibitor of human O-GlcNAcase (OGA) with a Ki of 5.9 μM, and it also displayed 28-fold selectivity for human OGA over human lysosomal β-hexosaminidase A (Hex A, Ki = 163 μM). In addition, cell-based assay revealed that this compound was cell-permeant and effectively induced cellular hyper-O-GlcNAcylation at 10 μM concentration.

O-Linked N-acetylglucosamine (O-GlcNAc) modification of serines/threonines on cytoplasmic proteins is a significant signal regulating cellular processes such as cell cycle, cell development, and cell apoptosis. O-GlcNAcase (OGA) is responsible for the removal of O-GlcNAc, and it thus plays a critical role in O-GlcNAc metabolism. Interestingly, OGA can be cleaved by caspase-3 into two fragments during apoptosis, producing an N-terminal fragment (1–413 a.a.), termed nOGA. Here, using 4-MU-GlcNAc (4-methylumbelliferyl 2-acetamido-2-deoxy-β-D-glucopyranoside) as substrate, we found that the nOGA fragment retains high glycosidase activity. To probe the role of nOGA in apoptosis, it is essential to develop a potent and specific nOGA inhibitor. However, many reported inhibitors active at nanomolar concentrations (including PUGNAc, STZ, GlcNAc-statin, and NAG-thiazoline) against full-length OGA were not potent for nOGA. Next, we screened a small triazole-linked carbohydrate library and first identified compound 4 (4-pyridyl-1-(2′-deoxy-2′-acetamido-β-D-glucopyranosyl)-1,2,3-triazole) as a potent and competitive inhibitor for nOGA. This compound shows 15-fold selectivity for nOGA (Ki = 48 μM) over the full-length OGA (Ki = 725 μM) and 10-fold selectivity over human lysosomal β-hexosaminidase A&B (Hex A&B) (Ki = 502 μM). These results reveal that compound 4 can be used as a potent and selective inhibitor for probing the role of nOGA in biological systems.

This communication describes a method for enzymatic preparation of bioactive glycans, which integrated the high-efficiency of homogenous phase enzymatic reaction and fast separation of solid phase extraction.

Inhibition of glycoside hydrolases has widespread application in treatment of diabetes, viral infections, lysosomal storage diseases and cancers. Gluco-configured tetrahydroimidazopyridines are the most potent β-glucosidase inhibitors reported to date. Using transition state mimic strategy, a series of C2-substituted gluco-configured tetrahydroimidazopyridines were designed and synthesized. Compounds 3 (Ki = 0.64 nM) and 5 (Ki = 0.58 nM) showed stronger inhibitory potency against β-glucosidase. Maestro 9.1 was used to study the structure–activity relationships by docking the compounds into the β-glucosidase active sites.

The Letter describes a strategy for the enzymatic synthesis of glycans based on a pH-responsive water-soluble polymer. In neutral condition, the polymer is water-soluble and convenient for in-solution enzymatic synthesis, whereas in acidic condition (pH lower than 4.0), the polymer disconnects with the product and becomes insoluble, which can be easily removed. A 6-Sialyl lactose analogue was synthesized as a model reaction using this approach.

Protein O-GlcNAcylation has been shown to play an important role in a number of biological processes, including regulation of the cell cycle, DNA transcription and translation, signal transduction, and protein degradation. O-GlcNAcase (OGA) is responsible for the removal of O-linked β-N-acetylglucosamine (O-GlcNAc) from serine or threonine residues, and thus plays a key role in O-GlcNAc metabolism. Potent OGA inhibitors are useful tools for studying the cellular processes of O-GlcNAc, and may be developed as drugs for the treatment neurodegenerative diseases. In this study, Cu(I)-catalyzed ‘Click’ cycloaddition reactions between glycosyl azides and alkynes were exploited to generate inhibitory candidates of OGA. Enzymatic kinetic screening revealed that compound 7 was a potent competitive inhibitor of human O-GlcNAcase (Ki = 185.6 μM). Molecular docking simulations of compound 7 into CpOGA (Clostridium perfringens OGA) suggested that strong π–π stacking interaction between the compound and W490 considerably contributed to improving the inhibitory activity.

This communication describes a method for enzymatic preparation of bioactive glycans, which integrated the high-efficiency of homogenous phase enzymatic reaction and fast separation of solid phase extraction.