Phosphates as Assisting Groups in Glycan Synthesis.

In nature, phosphates are added to and cleaved from molecules to direct biological pathways. The concept was adapted to overcome limitations in the chemical synthesis of complex oligosaccharides. Phosphates were chemically placed on synthetic glycans to ensure site-specific enzymatic elongation by sialylation.

Heparan Sulfate-Mimicking Glycopolymers Bind SARS-CoV-2 Spike Protein in a Length- and Sulfation Pattern-Dependent Manner.

Heparan sulfate-mimicking glycopolymers, composed of glucosamine (GlcN)-glucuronic acid (GlcA) repeating units, bind to the receptor-binding subunit (S1) and spike glycoprotein (S) domains of the SARS-CoV-2 spike protein in a length- and sulfation pattern-dependent fashion. A glycopolymer composed of 12 repeating GlcNS6S-GlcA units exhibits a much higher affinity to the S1 protein (IC = 13 ± 1.1 nM) compared with the receptor-binding domain (RBD).

VaporSPOT: Parallel Synthesis of Oligosaccharides on Membranes.

Automated chemical synthesis has revolutionized synthetic access to biopolymers in terms of simplicity and speed. While automated oligosaccharide synthesis has become faster and more versatile, the parallel synthesis of oligosaccharides is not yet possible. Here, a chemical vapor glycosylation strategy (VaporSPOT) is described that enables the simultaneous synthesis of oligosaccharides on a cellulose membrane solid support.

Heparan Sulfate Mimicking Glycopolymer Prevents Pancreatic β Cell Destruction and Suppresses Inflammatory Cytokine Expression in Islets under the Challenge of Upregulated Heparanase.

Diabetes is a chronic disease in which the levels of blood glucose are too high because the body does not effectively produce insulin to meet its needs or is resistant to insulin. β Cells in human pancreatic islets produce insulin, which signals glucogen production by the liver and causes muscles and fat to uptake glucose. Progressive loss of insulin-producing β cells is the main cause of both type 1 and type 2 diabetes.

On resin synthesis of sulfated oligosaccharides.

Sulfated glycans are involved in many biological processes, making well-defined sulfated oligosaccharides highly sought molecular probes. These compounds are a considerable synthetic challenge, with each oligosaccharide target requiring specific synthetic protocols and extensive purifications steps. Here, we describe a general on resin approach that simplifies the synthesis of sulfated glycans.

Visible-Light-Mediated Oxidative Debenzylation Enables the Use of Benzyl Ethers as Temporary Protecting Groups.

The cleavage of benzyl ethers by catalytic hydrogenolysis or Birch reduction suffers from poor functional group compatibility and limits their use as a protecting group. The visible-light-mediated debenzylation disclosed here renders benzyl ethers temporary protective groups, enabling new orthogonal protection strategies. Using 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) as a stoichiometric or catalytic photooxidant, benzyl ethers can be cleaved in the presence of azides, alkenes, and alkynes.

Facile triflic acid-catalyzed α-1,2--thio glycosylations: scope and application to the synthesis of -linked oligosaccharides, glycolipids, sublancin glycopeptides, and T/T antigens.

Studies of -linked glycoconjugates have attracted growing interest because of their enhanced chemical stability and enzymatic resistance over -glycoside counterparts. We here report a facile approach to access α-1,2--linked glycosides using triflic acid as a catalyst to promote the glycosylation of a series of thiols with d-glucosamine, galactosamine, glucose, and galactose electrophiles. This method is broadly applicable for the stereoselective synthesis of -linked glycopeptides, oligosaccharides and glycolipids in high yield and excellent α-selectivity.

Are Brønsted Acids the True Promoter of Metal-Triflate-Catalyzed Glycosylations? A Mechanistic Probe into 1,2--Aminoglycoside Formation by Nickel Triflate.

Metal triflates have been utilized to catalytically facilitate numerous glycosylation reactions under mild conditions. In some methods, the metal triflate system provides stereocontrol during the glycosylation, rather than the nature of protecting groups on the substrate. Despite these advances, the true activating nature of metal triflates remains unclear.

Real-time monitoring of solid-phase peptide synthesis using a variable bed flow reactor.

On-resin aggregation and incomplete amide bond formation are major challenges for solid-phase peptide synthesis that are difficult to be monitored in real-time. Incorporation of a pressure-based variable bed flow reactor into an automated solid-phase peptide synthesizer permitted real-time monitoring of resin swelling to determine amino acid coupling efficiency and on-resin aggregation.

Specific Inhibition of Heparanase by a Glycopolymer with Well-Defined Sulfation Pattern Prevents Breast Cancer Metastasis in Mice.

Heparanase, the heparan sulfate polysaccharide degrading endoglycosidase enzyme, has been correlated with tumor angiogenesis and metastasis and therefore has become a potential target for anticancer drug development. In this systematic study, the sulfation pattern of the pendant disaccharide moiety on synthetic glycopolymers was synthetically manipulated to achieve optimal heparanase inhibition. Upon evaluation, a glycopolymer with 12 repeating units was determined to be the most potent inhibitor of heparanase (IC = 0.

Glycosidase Inhibition by Multivalent Presentation of Heparan Sulfate Saccharides on Bottlebrush Polymers.

We report herein the first-time exploration of the attachment of well-defined saccharide units onto a synthetic polymer backbone for the inhibition of a glycosidase. More specifically, glycopolymers endowed with heparan sulfate (HS) disaccharides were established to inhibit the glycosidase, heparanase, with an IC value in the low nanomolar range (1.05 ± 0.

Design, synthesis, and evaluation of heparan sulfate mimicking glycopolymers for inhibiting heparanase activity.

Heparanase is an enzyme which cleaves heparan sulfate (HS) polysaccharides of the extracellular matrix. It is a regulator of tumor behavior, plays a key role in kidney related diseases and autoimmune diabetes. We report herein the use of computational studies to extract the natural HS-heparanase interactions as a template for the design of HS mimicking glycopolymers.

Utilization of bench-stable and readily available nickel(II) triflate for access to 1,2-cis-2-aminoglycosides.

The utilization of substoichiometric amounts of commercially available nickel(II) triflate as an activator in the reagent-controlled glycosylation reaction for the stereoselective construction of biologically relevant targets containing 1,2-cis-2-amino glycosidic linkages is reported. This straightforward and accessible methodology is mild, operationally simple and safe through catalytic activation by readily available Ni(OTf) in comparison to systems employing our previously in-house prepared Ni(4-F-PhCN)(OTf). We anticipate that the bench-stable and inexpensive Ni(OTf), coupled with little to no extra laboratory training to set up the glycosylation reaction and no requirement of specialized equipment, should make this methodology be readily adopted by non-carbohydrate specialists.

Synthesis of a polymerizable, bivalent glycan mimetic of the HIV envelope spike gp120.

A synthetic study on the creation of a bivalent, ROMP capable monomer has the ability to be polymerized into the corresponding neo-glycopolymer mimetic of the surface glycans on gp120 envelope spike of the HIV virus. In our approach, we have developed a new strategy for orthogonally attaching both the terminal Manα1-2Man disaccharide unit of the D1 arm of Man9GlcNAc2 of HIV gp120 and the terminal Manα1-2 unit of its D2 arm to a bivalent scaffold to produce the corresponding polymerizable monomer. The Manα1-2 saccharide moieties were assembled using a nickel catalyst, Ni(4-F-PhCN)(OTf), to activate trihaloacetimidate donors under mild and operationally simple procedure.

Comparison of manual therapy techniques with therapeutic exercise in the treatment of shoulder impingement: a randomized controlled pilot clinical trial.

The purpose of this double-blind, randomized controlled pilot study was to compare the effectiveness of four physical therapy interventions in the treatment of primary shoulder impingement syndrome: 1) supervised exercise only, 2) supervised exercise with glenohumeral mobilizations, 3) supervised exercise with a mobilization-with-movement (MWM) technique, or 4) a control group receiving only physician advice. Thirty-three subjects diagnosed with primary shoulder impingement were randomly assigned to one of these four groups. Main outcome measures included 24-hour pain (VAS), pain with the Neer and Hawkins-Kennedy tests, shoulder active range of motion (AROM), and shoulder function (SPADI).