For Research Use Only. Not for Clinical Use.

Creative Biolabs is a leading service provider that focuses on half-life extension for drug development. Based on our advanced platforms and extensive experience, now we can provide glycosylation-based half-life extension services for our clients all over the world.

Introduction of Glycosylation

In recent decades, a variety of therapeutic proteins and peptides has been developed against various indications, such as clotting factors, growth factors, hormones, enzymes, and antibodies. These proteins always present similar pharmacokinetic properties compared with their natural counterparts. However, their low molecular mass leads to terminal half-lives even below 1 day which largely limits their therapeutic applications. In this case, half-life extension strategies have been served as an integral part of development for many biotherapeutics.

For many therapeutic glycoproteins, N- or O-glycosylation occurs through posttranslational modifications and has important implications for half-life and in vivo efficacy. What's more, glycosylation can also affect the proteins' activity and binding properties. Glycosylation-based half-life extension has been a common approach in biochemistry research.

• N-glycosylation Based Half-Life Extension
  Half-life extension can be achieved through the introduction of additional N-glycosylation sites. Using the sequence NXTY or NXSY (X and Y are any amino acids except proline), N-glycosylation sites can be introduced. For example, hyperglycosylated erythropoietin contains two additional N-glycosylation sites and results in an extended half-life of approximately 3 days as well as Lower dosing frequency.
• O-glycosylation Based Half-Life Extension
  O-glycosylation is an alternative method to fuse or introduce sequences mediating O-glycosylation at hydroxyl groups of serine and threonine side chains. Compared with N-glycans, O-glycans are much smaller and have no specific sequons. In this case, known O-glycosylated regions from serum proteins are essential for O-glycosylation. For example, human chorionic gonadotropin (hCG) contains four O-glycosylation sites and a 28 amino acid-long carboxy-terminal peptide (CTP).

Fig 1. Increasing the negative charge of therapeutic peptides and proteins by the introduction of glycosylation sites or fusion to CTP can also prolong half-life. (Strohl, 2015)

• Carboxyl-Terminal Peptide (CTP) Based Half-Life Extension Service
  Carboxyl-terminal peptide (CTP) is the peptide with approximately 31 amino acid residues. In recent decades, CTP has been fused with a series of hormones, cytokines, and factors to obtain an extended half-life. For example, the CTP-fused erythropoietin (EPO) presents significantly improved half-life and improved in vivo efficacy compared with wild-type EPO. What's more, it presents good applicability for multiple peptides and proteins that has a wide range of applications

Features of Glycosylation Based Half-Life Extension

• Reduce clearance rate to extend the half-life.
• Improved pharmacokinetic and pharmacodynamic properties.
• Modulate the in vivo efficacy by altering the balance between potency and exposure time.

Creative Biolabs has been a long-term expert in the field of drug development. As a pioneer and the undisrupted global leader in half-life extension, we offer a variety of solutions to improve your productivity and streamline your research processes. If you are interested in our products or services, please do not hesitate to contact us for more detailed information.

Reference

1. Strohl, W. Fusion proteins for half-life extension of biologics as a strategy to make biobetters. BioDrugs. 2015, 29(4): 215-239.

Related Services:

• N-Glycosylation Based Half-Life Extension Service
• O-Glycosylation Based Half-Life Extension Service
• Carboxyl-Terminal Peptide (CTP) Based Half-Life Extension Service