Glycopeptide

BOC Sciences is a biological products and services provider offering a wide range of biotechnology services including peptide glycosylation. Our professional researchers are familiar with the latest research advances in the field of peptide glycosylation, and are able to provide professional advice and solutions to our customers. What's more, through quality control measures, we ensure that our clients receive satisfactory results.

Fig.1 Preparation of glycosylated peptides by direct and convergent strategies. (Moradi et al., 2016)

What are glycopeptides?

Glycopeptides represent a fascinating class of molecules wherein a carbohydrate (glycan) is covalently attached to a peptide chain. This conjugation imparts unique properties to the peptide, influencing its stability, bioactivity, and pharmacokinetic profile. The glycan component can vary widely, ranging from simple monosaccharides to complex oligosaccharides, and can be attached at specific amino acid residues within the peptide sequence.

Peptide glycosylation is a common post-transcriptional translational modification that occurs after protein synthesis. It can be carried out in an enzyme-catalyzed or non-enzyme-catalyzed manner. Enzyme-catalyzed peptide glycosylation occurs in the Golgi apparatus and endoplasmic reticulum and usually involves the concerted action of a series of enzymes. These enzymes are able to link the synthesized peptide chains with sugar molecules to form glycosylated peptides or glycosylated proteins. Peptide glycosylation plays an important biological function in organisms. It can affect protein folding, stability, cellular localization, and interactions with other molecules. Glycosylation can also regulate protein degradation rates, signaling and immune recognition.

Advantages of glycosylated peptides:

• Regulate the physical and chemical properties of peptide drugs and improve their absorption through biofilms.
• Glycosylated peptides can target specific organs.
• Enhance biological distribution in tissue.
• Improve permeability through biofilm.
• Increase metabolic stability and decrease clearance and receptor binding.
• Protect the side chains of amino acids from oxidation and maintain and stabilize the physical properties of peptides.

Glycopeptides mechanism of action

The mechanism of action of glycopeptides primarily revolves around their interaction with specific molecular targets. For instance, glycosylation can influence the binding affinity of peptides to receptors or other proteins, thereby altering their biological activity. In some cases, glycan moieties serve as recognition sites for cellular uptake or immune response modulation.

Notably, glycopeptides have been explored for their antimicrobial properties, particularly in the context of antibiotics like vancomycin and teicoplanin. These antibiotics function by inhibiting bacterial cell wall synthesis through binding to peptidoglycan precursors, a mechanism that is influenced by their glycosylation pattern.

In addition to antimicrobial activity, glycopeptides have shown promise in cancer therapy by targeting specific receptors on cancer cells or modulating immune responses against tumors. The glycan component can be tailored to optimize these interactions, leading to enhanced therapeutic efficacy.

Glycopeptides examples

Several noteworthy examples highlight the diversity and importance of glycopeptides in biomedicine. Vancomycin, a glycopeptide antibiotic, is a prominent example used clinically to treat infections caused by Gram-positive bacteria. Its mechanism of action involves binding to the D-alanyl-D-alanine terminus of bacterial cell wall precursors, disrupting cell wall synthesis.

Another significant glycopeptide is erythropoietin (EPO), a hormone essential for red blood cell production. Glycosylation of EPO is critical for its stability and biological activity, influencing its half-life in circulation and receptor binding affinity. This modification has been exploited in the development of therapeutic recombinant EPO for treating anemia.

In cancer immunotherapy, checkpoint inhibitors like nivolumab and pembrolizumab are glycopeptide-based biologics that target immune checkpoint receptors (e.g., PD-1) on T-cells, enhancing anti-tumor immune responses. Glycosylation plays a crucial role in modulating the binding interactions of these antibodies with their receptors.

Glycopeptide services

BOC Sciences, as a provider of glycosylation services, offers glycosylated peptides services, which include preparation and analysis of glycopeptide, and peptide glycosylation engineering services, etc. BOC Sciences is able to efficiently provide customers with products while offering a range of product analysis and testing services.

Services for synthesizing glycopeptides

BOC Sciences provides services for the synthesis of glycosylated peptides, including the synthesis of peptide chains with specific glycosylation sites and the attachment of sugar molecules to the corresponding amino acid residues.

Glycopeptide analysis

Mass spectrometry (MS) coupled with liquid chromatography (LC-MS) is a powerful tool for glycopeptide analysis, enabling precise determination of glycan composition, peptide sequence, and glycosylation site. Moreover, enzymatic cleavage using glycosidases or proteases facilitates the selective release of glycans or peptides, aiding in the characterization of glycopeptides. By integrating multiple analytical techniques, researchers can elucidate the intricate details of glycosylation patterns and their impact on peptide function.

a. Glycosylation specific antibody detection

BOC Sciences detects glycopeptides using specific antibodies, which can be achieved by techniques such as immunoblotting, immunohistochemistry and immunofluorescence staining.

b. Glycosylation zymography

Glycosylation zymography allows for the excision of glycosylated modifying enzymes using a glycosylase enzyme to produce a deglycosylated peptide. The deglycosylation product is then analyzed by mass spectrometry or other methods to determine the glycosylation site and type of glycosylation.

c. Glycosylation site prediction and bioinformatics analysis

Amino acid sequences of proteins or peptide chains are analyzed and predicted by bioinformatics tools and algorithms to identify potential glycosylation sites. These tools assess the likelihood of glycosylation of amino acid residues and provide probabilities for site prediction.

Peptide glycosylation engineering services

Peptide glycosylation engineering services offered by BOC Sciences include glycosylation site modulation, glycosyltransferase engineering, substrate engineering, and metabolic engineering.

a. Glycosylation site regulation

Through genetic engineering, amino acid residues in glycosylation sites are changed to specific glycosylation sites, or non-glycosylation sites are changed to glycosylation sites. This can modulate the glycosylation modification sites of peptides and change their glycosylation pattern.

b. Glycosyltransferase engineering

Genetically engineering the expression or activity of a glycosyltransferase enzyme to alter the type and extent of peptide glycosylation.

c. Substrate engineering

Modulation of the structure and sequence of a substrate peptide by genetic engineering to alter its substrate specificity for glycosyltransferases.

d. Metabolic engineering

Influencing the substrate supply and metabolic pathways for glycosylation modifications by modulating metabolic pathways and metabolite synthesis.

Why choose BOC Sciences?

• Development of therapeutic peptides using different glycosylation strategies
• High product yield and purity
• Strict validation and characterization
• Superior technical support: assist client from design to delivery
• Scale-up production up to kilograms

FAQ

1. Why is peptide glycosylation important in drug development?

Glycosylation can significantly impact the efficacy, safety, and pharmacological properties of peptide-based drugs. It can enhance protein stability, solubility, and serum half-life, as well as modulate immune response and cellular targeting.

2. How can peptide glycosylation improve therapeutic peptides?

Glycosylation can improve therapeutic peptides by increasing their resistance to enzymatic degradation, enhancing receptor binding affinity, and promoting targeted delivery to specific tissues or cells.

3. What analytical methods are used to characterize glycopeptides?

Common analytical methods include mass spectrometry (MS), liquid chromatography (LC), and glycan-specific enzymatic cleavage. These techniques enable precise determination of glycan composition, peptide sequence, and glycosylation site.

4. Can you customize glycosylation patterns for specific therapeutic purposes?

Yes, we can tailor glycosylation patterns to optimize peptide properties for specific therapeutic applications. Our experts work closely with clients to design and implement customized glycosylation strategies.

5. What types of peptides can benefit from glycosylation?

Various types of peptides, including antimicrobial peptides, hormone analogs, and antibody fragments, can benefit from glycosylation to improve their stability, activity, and pharmacokinetics.

6. How do you ensure the quality and consistency of glycosylated peptides?

We employ rigorous quality control measures throughout the glycosylation process, including analytical testing and validation at each stage. This ensures the production of high-quality and consistent glycosylated peptides.

7. What is the typical turnaround time for peptide glycosylation projects?

Turnaround times can vary depending on project complexity and scale. We work closely with clients to establish timelines that meet their specific needs and objectives.

8. Can you provide examples of successful glycosylation applications in drug development?

Examples include glycosylated antibiotics like vancomycin, which exhibit enhanced antimicrobial activity and reduced toxicity, as well as glycosylated hormone analogs like erythropoietin (EPO), which have improved pharmacokinetic profiles. Our analysis reports provide detailed insights into glycan composition, glycosylation sites, and quantitative data to support your research or development needs.