For Research Use Only. Not for Clinical Use.

Gelatin-like (GLK) protein is a group of biologically active recombinant polypeptide with extended in vivo half-life. GLK polypeptide sequence is not fixed, but generally has a strong hydrophilic. Protein drugs modified with GLK protein will greatly prolong its half-life. This method provides a rational and economical way of improving pharmacokinetic of protein drugs. Creative Biolabs is an outstanding service provider who offers the most comprehensive and professional GLK based half-life extension service to advance clients' projects.

Introduction of Gelatin-Like (GLK) Protein Based Half-Life Extension

Natural gelatin is the hydrolysis product of collagen widely used in the pharmaceutical industry as plasma expanders, stabilizers for vaccines, therapeutic implants, and other biopharmaceuticals. The GLK protein structure is modified from the natural gelatin, whose amino acid sequence is consisted of repeating Gly-X-Y triplets, where X and Y refer to any natural amino acid except cysteine, but they are often instead by proline. Since the amino acid sequence is not conserved, GLK structure has high flexibility. But similar to natural gelatin, most GLK protein is fairly hydrophilic, which leads to an increased hydrodynamic diameter, to some extent like hydrophilic polymers. Therefore, different GLK formulations prepared by genetic fusion different GLK formulations prepared by genetic fusion the serum half-life of target protein drugs.

Fig.1 Construction of the GLK/G-CSF expression vector. (Huang, 2010)

In contrast to other half-life extension strategies by recombinant polypeptide conjugation，GLK protein modifications closer to the PEGylation method in high hydrophilicity and low immunogenicity. Meanwhile, GLK protein modification avoids additional in vitro chemical modification processing, gives a higher yield, and reduces the manufacturing cost, has a broad application prospect.

Applications of Gelatin-Like (GLK) Protein Based Half-Life Extension

Many studies have shown that conjugate natural gelatin in proteins by chemical modification can improve their half-life, and the GLK protein based half-life extension is further developed on this basis. A half-life extending effect has been achieved recently by genetic fusion of a glycoprotein to an artificial GLK polypeptide aimed to fight leukemia. The study showed a 5.7-fold longer terminal plasma half-life of GLK-modified glycoprotein and similar in vivo bioactivity. Notably, after immunization of mice, an antibody response was only detected against heterologous domain but not against the GLK part. GLK modification has both effectiveness and low immunogenicity and can improve the half-life of target drugs while reducing side effects, which has great research and application value.

Highlights of GLK Protein Based Half-Life Extension Service

• Low immunogenicity, high safety
• Fairly hydrophilic, Maintain the water solubility of protein drugs
• Convenient and inexpensive, widely used in most pharmaceutical proteins
• Free of in vitro chemical modification.

GLK protein is a novel drug's half-life extension strategy and has developed rapidly in recent years. This method combined the advantages of PEGylation and carrier protein fusion technology while avoiding their disadvantages, has strong clinical application potential. If you are interested in our half-life extension service, please feel free to contact us for more information.

Reference

1. Huang, Y. S.; et al. Engineering a pharmacologically superior form of granulocyte-colony-stimulating factor by fusion with gelatin-like-protein polymer. European Journal of Pharmaceutics & Biopharmaceutics. 2010, 74(3), 435-441.