Glycan Remodeling Service

Various Glycan Remodeling Services at Creative Biolabs

Therapeutic antibodies are biological agents that modulate immune responses or directly intervene in disease processes by targeting specific biomolecules or cell surface receptors, which have important clinical applications and are widely developed as an important biopharmaceutical. Therapeutic antibody carries some heterogeneous glycans on their own protein structure, which affects the stability, immunogenicity, and efficacy of the antibody. Therefore, it is extremely important to perform glycoengineering-based glycan remodeling for therapeutic antibodies. Creative Biolabs has established a comprehensive and professional Glycoengineering Development Platform, and we provide a variety of strategies to support glyco-chemistry-based glycan remodeling.

• Strategy 1: Genetic engineering-based glycan remodeling service
  We synthesize specific glycosyl structures and introduce the glycosyl into the antibody structure through gene editing or transgenic technology, while combining specific glycoengineering enzymes to achieve the remodeling of glycans in organisms.
• Strategy 2: Chemical enzyme-based glycan remodeling service
  • Design of the solution: Different enzymes have different selectivities and reaction conditions for glycosyl groups. We select appropriate chemical enzymes to achieve glycan remodeling according to client needs and antibody characteristics.
  • Deglycosylation: We enzymatically deglycosylate antibodies using endoglycosidases.
  • Preparation of donor: We use chemical methods to synthesize the glycosyl derivatives that need to be remodeled as donors.
  • Glycan remodeling: The glycosyl donor is installed on the antibody protein under the catalysis of glycosynthase, thereby achieving glycan remodeling.

The method improves the ability to adjust protein glycosylation. The use of chemical enzymes for glycan remodeling can achieve precise glycosyl modification, providing support for the optimization of antibody drugs and personalized treatment. For example, we use α-2,6-sialyltransferase to sialylate IgG to generate the glycan composition of G2S1F and G2S2F, and use β-1,4-galactosyltransferase to galactosylate IgG to generate high levels of G2F glycans. In addition, we provide a variety of high-quality glycan-related products to assist and accelerate the in vitro glycosylation process of antibodies.

Table 1 List of glycan-related products we provide.

• Strategy 3: Solid-phase glycan remodeling (SPGR) service
  In addition, the in vitro activities of more glycoengineering enzymes are gradually becoming known, which provides new development strategies for glycan remodeling. For example, endoglycosidase S and its mutants were used to synthesize glycans and then replaced natural IgG glycans. Based on the principle of solid-phase peptide synthesis, we use SPGR technology to perform antibody glycoengineering services.
  • First, we design an appropriate glycoengineering strategy according to the antibody that needs to be modified and the desired glycosyl structure.
  • We select appropriate solid support materials as carriers, such as resins, for chemical modification on their surfaces to achieve glycosyl remodeling.
  • Then, We load the resin, immobilize the antibody, and perform steps such as washing, enzymatic glycan remodeling, and elution for efficient glycan remodeling. Moreover, the two processes of washing and enzymatic glycan remodeling can be repeated, thereby exchanging reaction buffers and enzymes. The antibody as substrate remains immobilized on the resin until all glycan remodeling processes are completed.
  • Finally, we isolate and purify the reconstituted antibodies, fluorescently label them, and perform mass spectrometry characterization to ensure that the obtained product meets the requirements.

Publication

Technology: Chemical enzymes

Journal: Methods In Enzymology

IF: 1.682

Published: 2017

Results: The authors chose the therapeutic monoclonal antibody Herceptin as a model for glycan remodeling using chemical enzymes. The results showed that Herceptin was remodeled into two glycoforms, namely the afucosylated complex glycoform and the fucosylated M9F glycoform, with the former exhibiting enhanced antibody-dependent cellular toxicity.

Fig.1 Glycan remodeling protocol of Herceptin.¹

Advantages

• Unique technology: We have mastered advanced glycosyl remodeling technology, which changes the glycosyl structure of antibodies and improves their efficacy and bioavailability.
• Custom service: We design and implement personalized glycosylation remodeling programs according to client needs to meet the specific requirements of different antibody projects.
• Efficient synthesis: We have an efficient glycosyl synthesis service, which can quickly synthesize complex glycosyl structures, and ensure the purity and stability of the synthesized products.

Applications

• Drug development: Glycosyl remodeling technology improves the efficacy, stability, and immunogenicity of biopharmaceuticals, thereby improving their therapeutic effect.
• Antibody engineering: Glycosyl remodeling can be used to change the glycosyl structure of the antibody, adjust the immunogenicity and activity of the antibody, and improve the bioavailability and efficacy of the antibody.
• Cell surface engineering: Glycosyl remodeling technology changes the glycosyl structure on the cell surface and regulates the signaling, adhesion, and recognition properties of cells.

Creative Biolabs has experienced and professional Antibody Glycoengineering teams to provide glyco-chemistry-based glycan remodeling services to clients around the world. We use glycosyl remodeling technology to regulate the immunogenicity of antibodies and reduce the risk of immune reactions, thereby improving therapeutic effects. Please contact us if you are interested in our glycan remodeling service.

Reference

1. Yang, Qiang, and Lai-Xi Wang. "Chemoenzymatic glycan remodeling of natural and recombinant glycoproteins." Methods In Enzymology. Vol. 597. Academic Press, 2017. 265-281.

Related Services:

1. Custom Glycosyl Linker Synthesis