Glycan Conjugation

Carbohydrate-Protein Conjugation

Peptide Glycosylation

Carbohydrate-Oligonucleotide Conjugation

Carbohydrate Lipid Conjugation

Glycan conjugation forms a pivotal link in biopharmaceutical research and development, harnessing the power of glycobiology to drive innovations. As a professional biotech company, BOC Sciences offers comprehensive glycan conjugation services. Our mission is to empower researchers, pharmaceutical professionals, and clinical laboratories with streamlined solutions of glycan conjugation, enabling them to further their understanding of various diseases, devise more effective treatments, and ultimately, enhance patient outcomes.

What are Glycans?

Glycans, also known as polysaccharides, are complex carbohydrates that are present in all living organisms. These molecules are composed of sugar units, typically including monosaccharides such as glucose, mannose, and galactose. Glycans can be highly branched or linear, and their diversity is further expanded by the presence of different sugar monomers. Glycans are chemically defined as polyhydroxy aldehydes, polyhydroxy ketones and their derivatives, or polymers that produce such compounds when hydrolyzed. They have a wide range of biological functions, including cell-cell interaction, immune response, inflammation, and are essential components of many biological molecules such as protein and lipids. They can be found in a free form or attached to other molecules, forming glycoproteins or glycolipids. Glycans can act as information carriers similar to nucleic acid and polypeptide chains. Glycan chains containing different structural information can covalently bond with proteins or lipids and form glycoconjugates.

Glycoconjugates

Glycan conjugation is a form of post-translational modification that involves adding glycan (saccharide) molecules to proteins, lipids, or other organic molecules to form glycoconjugates. This modification aids in the improved functioning of these biomolecules, increasing their stability, immunogenicity, and pharmacokinetics.

Glycoconjugates are the main components of cells, formed by the covalent conjugation of glycans with proteins, lipids, or other organic molecules, and are usually expressed on the cell surface. For example, glycans are linked to protein backbones through amino acid residues to form glycoproteins; glycans are linked to lipid components, such as glycerol, sphingolipids, or fatty acid esters to form glycolipids. Natural glycoconjugates play crucial roles in cellular communication, immune responses, and various physiological processes. The synthesis of glycoconjugates also has broad application prospects in biological research and therapy, including vaccines, glycan-based adjuvants, glycan conjugated antibodies, glycan-mediated drug delivery, etc.

Fig. 1 Glycoconjugates and their biological relevance. (Pergolizzi, G., 2016)

Advantages of Glycan Conjugation

Improved Drug Stability: Glycan conjugation can greatly increase the stability of biotherapeutics or drugs, allowing them to maintain their structure and function for a longer period of time. For example, glycans can shield therapeutic proteins from proteolytic enzymes, thereby improving their stability.

Controlled and Targeted Drug Delivery: Conjugation with specific glycan structures can allow a drug to be more effectively targeted to specific cells or tissues.

Reduced Immunogenicity: Some drugs can trigger a strong immune response, leading to side effects and reducing drug efficacy. Glycan conjugation can help to reduce the immunogenicity of these substances.

Improve Pharmacokinetics: Glycan conjugation can increase the solubility of bioactive compounds in water and improve their bioavailability and absorption rate. At the same time, it can prolong the biological half-life of therapeutic drugs in vivo, which means that drugs can stay in the system for a longer time, generating the advantages of administration and reducing the need for frequent administration, thus improving the compliance of patients.

Glycan Conjugation Services

Glycan bioconjugation can be distinguished according to the technology used to target carbohydrates, including:

• Glycan metabolism engineering.
• Glycotransferase treatment after glycan oxidation.
• Endoglycosidase.
• Ketone or azide labeling after transferase treatment.

BOC Sciences employs advanced chemical conjugation strategies, including reductive amination, hydrazide chemistry, glycosylamine formation, amidation, thiol-ene chemistry and click chemistry, ensuring precise and controlled glycan conjugation.

Our Competitive Advantages

• Allows the design of custom glycan conjugation strategies that meet the goals and specifications of a research or development effort
• Custom chemical conjugation and advanced enzymatic conjugation technology
• Elucidate glycoconjugate structures to ensure the accuracy of the conjugation process
• Ability to scale up the glycan conjugation process
• Integrating glycoconjugates into drug development
• Comprehensive quality control ensures the accuracy and stability of services
• Experienced expert technical team, with rich experience in the field of glycan conjugation
• The simplified polysaccharide combination service method enables us to provide results faster without affecting the quality
• Providing this highly specialized service at competitive prices

Case Study

• Case Study 1

Chemically modified allergens (allergoids) are hypoallergenic preparations widely used in allergen-specific immunotherapy (AIT) due to their excellent safety profile and clinical efficacy. The suitability of coupling allergoids to mannan by means of glutaraldehyde has been demonstrated for pollen and mite allergens. By using this methodology a remarkable structural stability of allergoids conjugated to mannan is achieved, which is an important issue from the perspective of vaccine development. Next, the in vivo immunogenicity of allergoids conjugated to nonoxidized mannan were assessed in different animal models. In rabbits, polymerized allergoids conjugated to mannan (PM) induced the production of potent IgG blocking antibodies. Humoral and cellular responses have been assessed in mice following subcutaneous or sublingual administration. By either route, PM was more efficient than native allergen extracts or polymerized allergoids, to increase IgG2a/IgE and IFN-γ/IL-4 ratios, reflecting a Th1-type driven response. Importantly, an increase of FOXP3⁺ Treg and IL-10-producing cells was observed in mice immunized with PM as compared with polymerized allergoids. Collectively, these data demonstrate that the better uptake of allergoids conjugated to nonoxidized mannan as well as the immunomodulating features exerted on DCs are observed for different allergen conjugates, DC subsets and animal species. Allergoids conjugated to nonoxidized mannan might well represent next generation vaccines that enhance the allergen uptake by DCs and promote healthy immune responses to allergens.

Fig.2 Steps for the generation and development of allergoids conjugated to mannan as vaccines for AIT. (Benito-Villalvilla, C., 2018)

• Case Study 2

Won et al. presented a switchable interface prepared by modifying AuNPs with polymeric "gates", which either allow the lectin to bind to the glycan present on AuNPs or not. Two different polymer chains were immobilized on the AuNPs with a size of 60 nm, a shorter one with an attached glycan and a longer one acting as an active gate. Under critical temperature, the longer polymer chain had an extended conformation with its shrinkage upon a shift of temperature above the critical value of 40 ℃, exposing underlying glycans. Lectins were detected with LOD down to µg/mL. The synthetic glycosylated nanoparticles that contain polymeric 'gates' to enable external control (via temperature changes) of glycan surface expression, as an alternative to enzymatic control in nature. This approach offers a new dynamic multivalent scaffold for glycan recognition.

Fig.3 (A) Synthesis of polymers by RAFT. (B) Concept of using responsive polymers to gate access to nanoparticles. (C) UV-Vis traces of different nanoparticle formulations in presence of serial dilution of lectin (1-10 µg/mL) after 30 min incubation at 20 ℃ or 40 ℃. (D) An increase in Abs700 and decrease in Abs540 is indicative of binding. TEM images of these particles after addition of lectin (E) at 20 ℃ for 30 min; (F) at 40 ℃ following 30 min incubation. (Won, S., 2017)

FAQ

1. How does glycan conjugation enhance the effectiveness of pharmaceutical drugs?

When glycans are attached to pharmaceutical drugs, they can significantly reduce the degradation rate of drugs, improve their stability, and enhance the body's immune response, ultimately leading to increased effectiveness of these drugs.

2. What types of drugs can benefit from glycan conjugation?

Many different types of drugs, especially proteins-based drugs, like antibodies and vaccines, can benefit from glycan conjugation. This is because glycan conjugation can modulate the behavior of these proteins in the body to improve their therapeutic effectiveness.

3. What techniques do you use for glycan conjugation?

We leverage both traditional and novel bioconjugation techniques including enzymatic and chemical conjugation methods. The choice of method depends on the structure and properties of the substance to be conjugated.

4. What quality controls do you have in place for your glycan conjugation services?

We follow stringent quality control measures to ensure the highest standard of our glycan conjugation services. These include rigorous checks throughout the conjugation process, detailed documentation for reproducibility, and state-of-the-art analytical services to verify the quality of the conjugates.

5. Is conjugation reversible?

Although the conjugation is typically designed to be stable and non-reversible under physiological conditions, there are certain enzymatic and chemical methods by which the conjugation can be reversed. However, the feasibility and success of de-conjugation largely depend on the specifics of the conjugate and method of attachment.

6. Does your company support customization in glycan conjugation services?

Absolutely. We understand that each project has unique requirements. Therefore, we offer personalized solutions and work closely with our clients to optimize the glycan conjugation process according to their specific needs.