Low-Background His-Tag-Targeting Probes for Turn-On Fluorescence Detection of Cell Surface Proteins and Their Binding Interactions.

Turn-on fluorescent probes consisting of dye-ligand conjugates serve as a powerful tool for detecting cell surface proteins (CSPs) and their interactions with binding partners. However, generating such probes from protein-based ligands remains challenging. This challenge became particularly evident during the COVID-19 pandemic, which highlighted the need for assays to evaluate inhibitors of the interaction between the SARS-CoV-2 virus receptor-binding domain (RBD) and the angiotensin-converting enzyme 2 (ACE2) receptor.

Amphiphilic Heparinoids as Potent Antiviral Agents against SARS-CoV-2.

Herein, we report the synthesis and biological evaluation of a novel series of heparinoid amphiphiles as inhibitors of heparanase and SARS-CoV-2. By employing a tailor-made synthetic strategy, a library of highly sulfated homo-oligosaccharides bearing d-glucose or a C5-epimer (i.e.

Fluorescent glyco-gold nanocluster induced EGFR mediated targeting of cancer cells.

A lot of attention has been focused on the functionalization of carbohydrate ligands on specific sizes and shapes of gold nanoparticles (AuNPs), where ultrasmall fluorescent AuNPs have not been well explored for direct imaging. Herein, we have engineered fluorescent gold nanoclusters with sulfated oligo-iduronic acid ligands (I34), which strongly bind to the HB-EGF receptor over FGF2, and regulate EGF receptor-mediated cancer cell homing in both two- and three-dimensional (2D and 3D) cell culture systems. These results offer a new practical and direct imaging tool for carbohydrate research.

Profiling Heparan Sulfate-Heavy Metal Ions Interaction Using Electrochemical Techniques.

Heparan sulfate glycosaminoglycans provides extracellular matrix defense against heavy metals cytotoxicity. Identifying the precise glycan sequences that bind a particular heavy metal ion is a key for understanding those interactions. Here, electrochemical and surface characterization techniques were used to elucidate the relation between the glycans structural motifs, uronic acid stereochemistry, and sulfation regiochemistry to heavy metal ions binding.

Targeting Selectins Mediated Biological Activities With Multivalent Probes.

Selectins are type-I transmembrane glycoproteins that are ubiquitously expressed on activated platelets, endothelial cells, and leukocytes. They bind to cell surface glycoproteins and extracellular matrix ligands, regulate the rolling of leukocytes in the blood capillaries, and recruit them to inflammatory sites. Hence, they are potential markers for the early detection and inhibition of inflammatory diseases, thrombosis, cardiovascular disorders, and tumor metastasis.

Sulfation Code and Conformational Plasticity of l-Iduronic Acid Homo-Oligosaccharides Mimic the Biological Functions of Heparan Sulfate.

Recently, the activity of heparan sulfate (HS) has led to the discovery of many drug candidates that have the potential to impact both medical science and human health. However, structural diversity and synthetic challenges impede the progress of HS research. Here, we report a library of novel l-iduronic acid (IdoA)-based HS mimics that are highly tunable in conformation plasticity and sulfation patterns to produce many of the functions of native HS oligosaccharides.

Rational designing of glyco-nanovehicles to target cellular heterogeneity.

The aberrant expression of endocytic epidermal growth factor receptors (EGFRs) in cancer cells has emerged as a key target for therapeutic intervention. Here, we describe for the first time a state-of-the-art design for a heparan sulfate (HS) oligosaccharide-based nanovehicle to target EGFR-overexpressed cancer cells in cellular heterogeneity. An ELISA plate IC inhibition assay and surface plasma resonance (SPR) binding assay of structurally well-defined HS oligosaccharides showed that 6--sulfation (6--S) and 6--phosphorylation (6--P) of HS tetrasaccharides significantly enhanced EGFR cognate growth factor binding.

Discovery of rare sulfated -unsubstituted glucosamine based heparan sulfate analogs selectively activating chemokines.

Achieving selective inhibition of chemokines with structurally well-defined heparan sulfate (HS) oligosaccharides can provide important insights into cancer cell migration and metastasis. However, HS is highly heterogeneous in chemical composition, which limits its therapeutic use. Here, we report the rational design and synthesis of -unsubstituted (NU) and -acetylated (NA) heparan sulfate tetrasaccharides that selectively inhibit structurally homologous chemokines.

Synthetic heparan sulfate ligands for vascular endothelial growth factor to modulate angiogenesis.

We report the discovery of a potential heparan sulfate (HS) ligand to target several growth factors using 13 unique HS tetrasaccharide ligands. By employing an HS microarray and SPR, we deciphered the crucial structure-binding relationship of these glycans with the growth factors BMP2, VEGF, HB-EGF, and FGF2. Notably, GlcNHAc(6-O-SO)-IdoA(2-O-SO) (HT-2,6S-NAc) tetrasaccharide showed strong binding with the VEGF growth factor.

Heparan Sulfate Mimetics Differentially Affect Homologous Chemokines and Attenuate Cancer Development.

Achieving selective inhibition of chemokine activity by structurally well-defined heparan sulfate (HS) or HS mimetic molecules can provide important insights into their roles in individual physiological and pathological cellular processes. Here, we report a novel tailor-made HS mimetic, which furnishes an exclusive iduronic acid (IdoA) scaffold with different sulfation patterns and oligosaccharide chain lengths as potential ligands to target chemokines. Notably, highly sulfated-IdoA tetrasaccharide () exhibited strong binding to CCL2 chemokine thereby blocking CCL2/CCR2-mediated cancer cell invasion and metastasis.

Continuous-Flow Accelerated Sulfation of Heparan Sulfate Intermediates.

We report for the first time a continuous-flow strategy to execute -sulfation modification of heparan sulfate (HS) oligosaccharides. A systematic investigation of the influence of the flow parameters on the installation of the sulfate group on glucosamine monosaccharide can aid the development of a comprehensive, quick, and reliable strategy for -sulfation of HS oligosaccharide precursors. Deprotection of the sulfated heparin intermediates led to the development of a comprehensive biologically inspired oligosaccharide library to understand the crucial structure-function relationship of HS.

ABO Antigens Active Tri- and Disaccharides Microarray to Evaluate C-type Lectin Receptor Binding Preferences.

Understanding blood group antigen binding preferences for C-type lectin receptors holds promise for modulating immune responses, since several Gram-negative bacteria express blood group antigens as molecular mimicry to evade immune responses. Herein, we report the synthesis of ABO blood group antigen active tri and disaccharides to investigate the binding specificity with various C-type lectin receptors using glycan microarray. The results of binding preferences show that distinct glycosylation on the galactose and fucose motifs are key for C-type lectin receptor binding and that these interactions occur in a Ca-dependent fashion.