For Research Use Only. Not for Clinical Use.

Creative Biolabs has long-lasting expertise in the design and conduct of novel drug molecules. Based on our advanced platforms and extensive experience, now we can provide PASylation-based half-life extension services for our clients all over the world.

Introduction of PAS Polymers

In modern drug treatment, the most limitation for therapeutic peptides and proteins is the fast clearance via kidney filtration. PAS polymers refer to the novel polypeptides composed of the small amino acids Pro, Ala, and Ser. They are polypeptide chains with expanded hydrodynamic volume. Like polyethylene glycol (PEG), PAS polymers present biophysical properties such as hydrophilic, highly soluble, and uncharged. At the genetic level, PAS polymers can be fused with therapeutic proteins or polypeptides, thereby producing fully active fusions in E. coli and avoiding cumbersome in vitro coupling or modification steps. PASylation is a novel technology that enables the generation of therapeutic peptides/proteins with an extended half-life.

Fig 1. Concept of PASylation. Modeled structure of the PASylated Fab fragment of an antibody and the comparison of the chemical composition between the synthetic linear polymer PEG. (Schlapschy, 2013)

Applications of PASylation in Half-Life Extension

In recent years, PAS polymers have been widely used in a variety of therapeutic peptides and proteins, such as hormones, cytokines, enzymes, as well as antibody fragments. By changing the length of the PAS polymer, the half-life of biopharmaceuticals can be specifically adjusted. Studies have shown that the half-life of PASylation proteins with 30-200 PAS polymer repeats is extended by 2-90 times compared with wild-type proteins. The half-life of all Fab-PAS combinations is much longer than that of unmodified Fab. When the length of the PAS peptide is increased from 100 to 600 residues, the half-life of the Fab-PAS combination can be extended from 2.71 hours to 28.19 hours. What's more, a PAS polymer containing 600 residues (PAS600) can extend the half-life of the interferon superagonist YNSα8 from 3 hours to 30 hours, and no loss of biological potency was detected in mice.

Advantages of PASylation in Half-Life Extension

• Fusion expression is allowed to avoid tedious in vitro coupling or modification steps.
• Biodegradable to avoid organ accumulation.
• Resistant to serum proteases and demonstrates stability in serum.
• Can be applied in both microbial and eukaryotic host organisms.
• No toxicity or immunogenicity in mice.

Based on long-term expert in the field of drug development, Creative Biolabs provides a variety of solutions to fit your specific research needs. If you are interested in our products or services, please do not hesitate to contact us for more detailed information.

Reference

1. Schlapschy, M.; et al. PASylation: a biological alternative to PEGylation for extending the plasma half-life of pharmaceutically active proteins. Protein Engineering, Design & Selection. 2013, 26(8): 489-501.