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 a series of half-life extension services by carbohydrate modification for our clients all over the world.

Why Carbohydrate Modification?

In recent decades, PEGylation is always the most successful approach to protract the half-life of peptides and proteins. According to statistics, more than 12 biopharmaceuticals based on PEGylated peptides and proteins have been approved for marketing. However, the biocompatibility of the large PEG polymers remains problems especially for chronic treatment, while there is no mechanism to completely degrade PEG into components useful for metabolism in humans. In this case, the novel bio-compatible PEG mimetics are necessary to avoid the risks of long-term toxicity of biopharmaceuticals. For example, carbohydrate modification.

Fig 1. Reducing renal clearance of a peptide or protein by increasing its molecular size has been proven to be an effective way to prolong the half-life. (Tan, 2018)

• Glycosylation Based Half-Life Extension
  For a variety of therapeutic glycoproteins, N- or O-glycosylation occurs through posttranslational modifications and has important implications for half-life and in vivo efficacy. Using the sequence NXTY or NXSY (X and Y are any amino acids except proline), N-glycosylation sites can be introduced to extend the half-life. O-glycosylation is an alternative method to fuse or introduce sequences mediating O-glycosylation at hydroxyl groups of serine and threonine side chains.
• Polysialylation Based Half-Life Extension Service
  Polysialylation refers to the process that polysialic acid (PSA) is conjugated to drugs for the improvement of pharmacokinetic properties. Colominic acid (CA) is the only observed PSA variant in humans. CA is a naturally occurring polysaccharide that plays important role in cell-cell adhesion and synaptic plasticity. The reductive amination strategy has been the most widely used method for polysialylated drugs production. In addition, the chemoselective maleimide-thiol conjugation reaction and chemo-enzymatic method can also be used to produce polysialylated proteins.
• Other Polysaccharide Based Approaches
  Dextran conjugation and HESylation are most similar to PEGylation, both of these two techniques increase the hydrodynamic radius of the target molecule to reduce renal excretion and thereby extend the half-life of the therapeutic proteins. In contrast, the PSA and HA polymers contain multiple negative charges. In addition to increasing molecular weight, electrical rejection can further reduce its renal clearance, thereby prolonging its half-life. What's more, the negative charges also increase water solubility to the biopharmaceuticals.

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. Tan, H.; et al. Recent advances in half-life extension strategies for therapeutic peptides and proteins. Current pharmaceutical design. 2018, 24(41): 4932-4946.

Related Services:

• Glycosylation Based Half-Life Extension Service
• Polysialylation Based Half-Life Extension Service
• Other Polysaccharide Based Approaches