Compositions and Functions of Dermatan Sulfate (DS)

DS belongs to Glycosaminoglycans, composed of a repeating disaccharide unit containing iduronic acid (IdoA) and N-acetylgalactosamine (GalNAc). However, the DS polysaccharide chain is heterogeneous with multiple sugar and sulfation patterns as it is biosynthesized from chondroitin or Chondroitin Sulfate chains by random enzymatic modifications such as C-5 isomerization and O-sulfation. DS usually binds to a core protein and forms a corresponding glycoprotein, DS-proteoglycan (DS-PG). DS-PG is a component of the cell surface and extracellular matrix and is involved in tumorigenesis and metastasis, neurological development, viral adsorption and infections, and atherosclerosis.

Fig.1 Graphical representation of diseases related to DS. (Zhang & Chi, 2021)

DS-based Cell Surface Glycoengineering Service at CD BioGlyco

DS is involved in many physiological and pathological processes, and an accurate understanding of the mechanism of DS in these processes will facilitate the development of DS polysaccharide drugs as well as the application of clinical therapy. Currently, we provide analytical services for the molecular mechanisms and binding motifs of multiple gag-protein complexes for characterizing gag-protein interactions and their applications in DS-PG. we offer the following services:

• Modification service

We intervene in the biosynthesis by enzymatic modifications such as C-5 isomerization and O-sulfation to add different sulfation patterns. Furthermore, we provide sulfation modification services at the hydroxyl groups at positions GalNAcC4 and C6 and the GlcA / IdoA residues at position C2. We modulate the hypersulfation pattern of CSPGs by an in vitro experimental service. To assess the adsorption and invasion of pathogens on the host cell surface for DS motifs with specific patterns of sulfation modification.

• Affinity analysis service

Many affinity-based analytical techniques and tools are used to explore the role of biomolecular interactions in physiological and pathological phenomena. CD BioGlyco provides affinity chromatography, Gel Mobility Shift Assay (GMSA), Isothermal Titration Calorimetry (ITC), and biosensor-based Surface Plasmon Resonance (SPR) technology services. We isolate DS from mixtures by binding highly specific macromolecules between DS and target proteins via affinity chromatography, while we use ITC for the characterization of GAG-binding motifs.

• Other services

• Microarray analysis service

CD BioGlyco provides high sensitivity and throughput glycan chip analysis DS services. Comparing the binding strength between ligand oligosaccharides, looking for specific oligosaccharide ligands, and improving DS bioactive applications.

• Mass spectrometry (MS) analysis service

CD BioGlyco provides MS analysis for the characterization of DS complexes mainly including surface marker MS, crosslinking MS, ion mobility (IM) mass spectrum, and recently emerged natural mass spectrum. with high sensitivity, tolerance to low-purity samples, and the ability to identify single amino acid/sugar residues and modifications. It has mature applications in DS sequence localization, protein epitope positioning, and DS binding protein structure characterization.

• NMR analysis service

CD BioGlyco offers available NMR analysis services including chemical shift perturbation, saturation transfer difference, and transfer nuclear spillover effect. The analysis service provides information about the conformational changes in the DS upon interaction with proteins by identifying protein-induced changes in NOE signaling in the ligand molecule.

Fig.2 DS-based cell surface glycoengineering analysis service. (CD BioGlyco)

Applications of DS-based Cell Surface Glycoengineering

• DS-based cell surface glycoengineering serves as a target for drug development and therapy in breast cancer by inducing necrotizing apoptosis.
• DS-based cell surface glycoengineering can be used as a modulator of tissue and cell development.
• DS-based cell surface glycoengineering mediates the intracellular release of natural anti-inflammatory tripeptides to regulate the inflammatory response of the endothelium, application in the treatment of vascular diseases.
• Modified DSPGs promote inflammatory responses by binding immune receptors like toll-like receptors, selectin, CD44, and β-1 integrins, which help to drive the treatment of traumatic brain/spinal cord injury and multiple sclerosis.
• Modified DS-based cell surface glycoengineering plays an important role in lipid retention, modification, and final accumulation.
• In addition, DS-based cell surface glycoengineering promotes wound healing and improves osteoarthritis.

Advantages

• Integrating multiple large-scale instruments makes the structural characterization of DS and protein interaction analysis easy.
• Combined with the Glycoengineering Platform, our professional talent team provides customized sugar-based services according to customer requirements.

CD BioGlyco provides high-quality Cell Surface Glycoengineering Services to our clients. We are recognized for providing high-quality services to customers in many countries. Please feel free to contact us, and we will reply to you as soon as possible.