The Features of Heparan Sulfate (HS)

The precursor HS chain is a non-sulfated multimer initially synthesized in Golgi bodies. HS is a linear polysaccharide consisting of a characteristic repeating sequence with repeating disaccharide units (GlcUAβ1-4GlcNAcα1-4)_n. The HS is linked to and polymerizes with adjacent serine (Ser) residues in the Ser-Gly dipeptide sequence of the core protein, and hydrophobic amino acids and acidic amino acids at the C-terminus of the Ser-Gly sequence. The fine structure of the HS chain determines its functional properties because the binding of many specific ligands to HS depends on the form of HS modification. HS regulates cell adhesion, proliferation, migration, and differentiation and influences the onset, progression, and outcome of pathophysiological processes such as development, tissue repair, inflammation, infection, and tumorigenesis.

Fig.1 Schematic overview of the function of cell surface HS proteoglycans. (Hayashida, et al., 2022)

HS-based Cell Surface Glycoengineering Service at CD BioGlyco

Almost all the cells of eukaryotic and multicellular organisms express one or several heparan sulfate proteoglycans (HSPGs) on their cell surface. For the HS-based on the cell surface, we provide the following services:

• The modified forms of HS-based cell surfaces are highly regulated by the properties of the enzymes synthesized by HS and their encoded forms. Unmodified HS is modified by N-deacetylation, N-sulfonation, heteropolymerization, and several O-sulfonation reactions catalyzed by different membrane-bound enzymes. We mainly provide the following several enzyme modification services including N-sulfonyltransferase, 2-O-sulfonyltransferase, 6-O-sulfonyltransferase, 3-O-sulfonyltransferase, and glyonyl C5-epitope isomerase.
• CD BioGlyco provides various services to extract the HS on the cell surface and analyze its structure. We provide various methods such as liquid chromatograph mass spectrometer (LC-MS), electrospray ionization (ESI) mass spectrometry (ESI-MS), and MSⁿ for the structural characterization of glycans.
• According to genetic research, there are at least 20 genes involved in the aggregation and modification of HS. We provide a variety of services applied to a single or combination of fund knockout services to clients with the most convenient gene editing services.
• Cell surface HS nonspecifically promotes receptor complex formation either via allosteric or bridging mechanisms and affects multimerization and stabilization of the ligand. CD BioGlyco provides HS nonspecific binding to ligand-receptor interactions and its resulting signaling services.

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

Publication

Paper Title: Changes in heparan sulfate sulfotransferases and cell-surface heparan sulfate during SKM-1 cells granulocytic differentiation and A549 cells epithelial-mesenchymal transition

Technology: Flow cytometry, Gene knock-out, Western blot

Journal: Glycoconjugate Journal

IF: 3.1

Published: 2020

Results: HS 2-O sulfotransferase in mRNA and protein levels were down-regulated during granulocyte differentiation of SKM-1 leukemia cells, and epithelial glucosamine HS 3-O sulfotransferase 3A (HS3ST3A). The cell surface by antibody recognition, was observed in A549 lung cancer cells. In addition, HS3ST3A was negatively correlated with the in vitro cellular metastatic ability of A549 cells, as confirmed by RNA interference techniques, wound healing assays, and in vitro Matrigel invasion assays. In conclusion, specific HS molecules are of interest as molecular drugs and targets for the development and treatment research of cancer diseases.

Fig.3 ATRA-induced granulocytic differentiation of MDS leukemia SKM-1 cells. (Zhao & Wang, 2020)

Applications of HS-based cell surface glycoengineering

• HS is released from cell particles in response to injury. The modified HS-based cell surface glycoengineering subsequent entry into the serum leads to inhibition of blood coagulation, and the heparin injection solution is clinically utilized for anticoagulant therapy.
• The glycosylated modified HS-based cell surface glycoengineering plays a key role in the treatment and drug development of multiple genetic diseases.
• The modified HS-based cell surface glycoengineering interacts with molecules with abundant, strong anions non-specifically with growth factors and extracellular matrix (ECM) components to protect the ligand from enzymatic digestion and retention.
• The modified HS-based cell surface glycoengineering is suitable for the screening of specific ligands and functional property expression studies.

Advantages

• Our company provides comprehensive cell surface HS modification and analysis services.
• With the Glycoengineering Platform and trained technicians, we offer customized Cell Surface Glycoengineering services to our clients.

CD BioGlyco provides several Cell Surface Glycosaminoglycans (GAG) Glycoengineering Service. Moreover, we provide efficient Chondroitin Sulfate (CS), Dermatan Sulfate (DS), Keratan Sulfate (KS), and Hyaluronic Acid (HA) glycoengineering services. We are committed to being your first choice in the field of glycobiology research. If you are interested in our service, please contact us further to introduce the specific service in detail.