For Research Use Only. Not for Clinical Use.

Creative Biolabs is a leading service provider that focuses on the design and conduct of novel drug molecules. Based on our advanced platforms and extensive experience, now we provide recombinant polypeptide conjugation-based half-life extension services for our clients all over the world.

Introduction of Half-life Extension

Therapeutic peptides and proteins present great potentials for diseases treatment. Indeed, the natural ligands always present superior drug properties, including efficient receptor binding and safety. However, the rapid metabolism and proteolytic degradation result in very short systemic half-lives, even in the range of minutes to few hours.

In general, the half-life of peptide/protein drugs depends not only on the receptor-mediated recycling system but also on the effect of renal clearance of large molecular size. In this case, a variety of half-life extension techniques have been developed. Arguably, PEGylation is the most common approach but always limited by safety, such as hypersensitivity reactions, antibody formation, as well as PEG bioaccumulation. Now the recombinant unstructured polypeptides have been alternatives to PEGylation.

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)

• XTEN Based Half-Life Extension
  XTEN polymers are a class of unstructured polypeptides composed of six hydrophilic and chemically stable amino acids A, E, G, P, S, and T. The extended and unstructured conformation of XTEN allows a large hydrodynamic volume. A series of experimental data showed that XTEN-protein exhibits an extended half-life with multiple advantages.
• ELPylation Based Half-Life Extension
  Elastin-like polypeptides (ELPs) are a class of stimulus-responsive biomaterials composed of short repeating peptide motifs containing VPGXP, where X is a guest residue that can be any amino acid except proline. The transition temperature (Tt) of ELPs can be adjusted by changing the guest residues and the length of the ELPs.
• PASylation Based Half-Life Extension
  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 that can be fused with therapeutic proteins or polypeptides. PASylation is a novel technology that enables the generation of therapeutic peptides/proteins with an extended half-life.
• HAPylation Based Half-Life Extension
  The active molecule of HAPylation is a repeated sequence of a glycine-rich (Gly₄Ser)_n polypeptide. Studies have shown that HAPylation can increase Fab's half-life in the animal model. The increase in chain length will greatly reduce the solubility of HAP.
• Gelatin-Like Protein (GLK) Based Half-Life Extension
  Gelatin-like protein (GLK) is a group of the biologically active recombinant polypeptide has a (Gly-XY)_n structure, where X and Y refer to any natural amino acid except Cys and n stands between 60 and 1500 amino acid residues. This construct has been used for in vivo half-life extension.

As an extension of your laboratory, our team customizes services and solutions to your specific needs. 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:

• XTEN Based Half-Life Extension Service
• ELPylation Based Half-Life Extension Service
• PASylation Based Half-Life Extension Service
• HAPylation Based Half-Life Extension Service
• Gelatin-Like (GLK) Protein Based Half-Life Extension Service