Automated glycan assembly of highly branched heptadecasaccharide repeating unit of arabinogalactan polysaccharide HH1-1 from .

Polysaccharides that are part of the human diet of fruits and vegetables influence the immune system multiple signaling pathways. Given the immense complexity and diversity of naturally occurring polysaccharides and the difficulties associated isolating pure samples, few structure-activity relationships have been established. Rapid access to well-defined polysaccharides of biological relevance by automated glycan assembly (AGA) is important to create chemical tools to determine the link between nutritional oligo- and polysaccharides and the immune response.

Automated Synthesis of Chondroitin Sulfate Oligosaccharides.

Glycosaminoglycans (GAGs) are important sulfated carbohydrates prevalently found in the extracellular matrix that serve many biological functions. The synthesis of structurally diverse but defined GAGs is extremely challenging as one has to account for the various sulfation patterns. Described is the automated synthesis of chondroitin sulfate hexasaccharides on a solid support equipped with a photolabile linker.

Automated Glycan Assembly of Oligogalactofuranosides Reveals the Influence of Protecting Groups on Oligosaccharide Stability.

Galactofurans are an important structural constituent of arabinogalactan and lipopolysaccharides (LPS) ubiquitously present on the envelopes of all . Key to the automated glycan assembly (AGA) of linear galactofuranosides as long as 20-mers was the identification of thioglycoside building blocks with a fine balance of stereoelectronic and steric effects to ensure the stability of oligogalactofuranoside during the synthesis. A benzoylated galactofuranose thioglycoside building block proved most efficient for oligosaccharide construction.

Trisaccharide Sulfate and Its Sulfonamide as an Effective Substrate and Inhibitor of Human Endo--sulfatase-1.

Human endo--sulfatases (Sulf-1 and Sulf-2) are extracellular heparan sulfate proteoglycan (HSPG)-specific 6--endosulfatases, which regulate a multitude of cell-signaling events through heparan sulfate (HS)-protein interactions and are associated with the onset of osteoarthritis. These endo--sulfatases are transported onto the cell surface to liberate the 6-sulfate groups from the internal d-glucosamine residues in the highly sulfated subdomains of HSPGs. In this study, a variety of HS oligosaccharides with different chain lengths and - and -sulfation patterns via chemical synthesis were systematically studied about the substrate specificity of human Sulf-1 employing the fluorogenic substrate 4-methylumbelliferyl sulfate (4-MUS) in a competition assay.

An integrated microfluidic system for rapid detection and multiple subtyping of influenza A viruses by using glycan-coated magnetic beads and RT-PCR.

The influenza A (InfA) virus, which poses a significant global public health threat, is routinely classified into "subtypes" based on viral hemagglutinin (HA) and neuraminidase (NA) antigens. Because there are nearly 200 viral subtypes, current diagnostic approaches require multiplexing or array systems to cover various subtypes of HA and NA. A microfluidic chip featuring a HA × NA array was consequently developed herein for diagnosis and subtyping of InfA viruses via the use of glycan-coated magnetic beads followed by reverse transcription (RT) polymerase chain reaction (PCR).

Exploring eukaryotic prokaryotic ribosomal RNA recognition with aminoglycoside derivatives.

New derivatives of aminoglycosides containing 6'-carboxylic acid or 6'-amide on their ring I were designed, synthesized and their ability to readthrough nonsense mutations was examined , along with the protein translation inhibition in prokaryotic and eukaryotic systems. The observed structure-activity relationships, along with the comparative molecular dynamics simulations within the eukaryotic rRNA decoding site, showed high sensitivity of 6'-position to substitution, indicating that the rational design of potent stop-codon read-through inducers requires consideration of not only the structure and energetics of the drug-RNA interaction but also the dynamics associated with that interaction.

"One-Pot" Protection, Glycosylation, and Protection-Glycosylation Strategies of Carbohydrates.

Carbohydrates, which are ubiquitously distributed throughout the three domains of life, play significant roles in a variety of vital biological processes. Access to unique and homogeneous carbohydrate materials is important to understand their physical properties, biological functions, and disease-related features. It is difficult to isolate carbohydrates in acceptable purity and amounts from natural sources.

Yb(OTf)-Catalyzed Desymmetrization of myo-Inositol 1,3,5-Orthoformate and Its Application in the Synthesis of Chiral Inositol Phosphates.

A variety of inositol phosphates including myo-inositol 1,4,5-trisphosphate, which is a secondary messenger in transmembrane signaling, were selectively synthesized via Yb(OTf)-catalyzed desymmetrization of myo-inositol 1,3,5-orthoformate using a proline-based chiral anhydride as an acylation precursor. The investigated catalytic system could regioselectively differentiate the enantiotopic hydroxy groups of myo-inositol 1,3,5-orthoformate in the presence of a chiral auxiliary. This key step to generate a suitably protected chiral myo-inositol derivatives is described here as a unified approach to access inositol phosphates.

Design of Novel Aminoglycoside Derivatives with Enhanced Suppression of Diseases-Causing Nonsense Mutations.

New pseudotrisaccharide derivatives of aminoglycosides that exploit additional interaction on the shallow groove face of the decoding-site rRNA of eukaryotic ribosome were designed, synthesized and biologically evaluated. Novel lead structures (6 and 7 with an additional 7'-OH), exhibiting enhanced specificity to eukaryotic cytoplasmic ribosome, and superior nonsense mutation suppression activity than those of gentamicin, were discovered. The comparative benefit of new leads was demonstrated in four different nonsense DNA-constructs underling the genetic diseases cystic fibrosis, Usher syndrome, and Hurler syndrome.

Nano-CuFe2O4 as a magnetically separable and reusable catalyst for the synthesis of diaryl/aryl alkyl sulfides via cross-coupling process under ligand-free conditions.

An efficient protocol was developed for the CuFe(2)O(4) nanopowder-catalyzed aryl-sulfur bond formation between aryl halide and thiol/disulfide. A variety of aryl sulfides were synthesized in impressive yields with good chemoselectivity and functional group tolerance in the presence of a catalytic amount of CuFe(2)O(4), Cs(2)CO(3) as base, in nitrogen atmosphere, under ligand-free conditions, in DMSO as solvent at 100 °C. The catalyst is air-stable, inexpensive, magnetically separable and recyclable up to four cycles.

Recyclable heterogeneous copper oxide on alumina catalyzed coupling of phenols and alcohols with aryl halides under ligand-free conditions.

An efficient alumina-supported CuO-catalyzed O-arylation of phenols and aliphatic alcohols with various aryl as well as heteroaryl halides under ligand-free conditions are reported. This protocol provides a variety of diaryl ether and bis-diaryl ether motifs by reacting different aryl/aliphatic halides with differently substituted phenols and saturated alcohols in the presence of a catalytic amount of CuO on alumina and KOH as a base at moderate temperature under nitrogen atmosphere. The described methodology is simple, straightforward and efficient to afford the cross-coupled products in high yields under ligand-free conditions.