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In the past years, much attention has been focused on peptides and small protein scaffolds that are emerging as safe therapeutics. Extending the half-life of drugs by the conjugation to albumin has become a hot spot. Creative Biolabs is a leading service provider in half-life extension services.

Background of Lipidation

Peptides and small protein scaffolds are emerging as safe therapeutics. They have a wide range of properties similar to full-length antibodies, high affinity with ligands, excellent target specificity, low toxicity, and a relatively small mass that small enough to diffuse into tissues. Despite being quite effective, small biotherapeutics can have a relatively short circulating half-life that limits their applications. For this reason, numerous effective half-life extension strategies have been generated against this limitation in the last decades. A ponderable method to extend the circulating half-life of the peptides and small protein drugs is conjugation to albumin, the most plentiful serum protein exhibits an average half-life of 19 days. Lipidation refers to peptides and proteins conjugated with human serum albumin (HSA) in a non-covalent way via fatty acid binding.

Fig.1 Tertiary structure of albumin binding of some ligands. (Quinlan, 2005)

This method has been proven to be one of the most successful approaches for the development of biotherapeutics with effective pharmacokinetic properties and excellent efficacy. There are nine different fatty acid binding sites in HSA, which not only have fatty acid recognition functions but may also have binding functions of fatty acids conjugated to larger molecules. Therefore, peptide lipidation promotes albumin interactions and can be developed into a method for the improvement of the pharmacokinetic properties of peptide pharmaceuticals. Early trials were applied to extend the half-life of peptide and protein drugs with small albumin-binding tags, and insulin detemir is the first molecule of this type. Saturated fatty acids might combine with serum albumin via weak affinities. The albumin-binding fatty acid tail further extends the half-life of the drug.

Fig.2 Different ways to connect to albumin (Bech, 2018)

Innovative Ways of Lipidation

Some studies have discovered an albumin-binding ligand, which based on the chimera combines peptides and fatty acids. In the ligand, a fatty acid will be bound to a short peptide due to the existence of an amino acid chain. The fatty acid will conjugate to albumin with a tiny affinity and the peptide moiety might increase the affinity by forming additional interactions to albumin. More importantly, this albumin ligand might extend the half-life of peptides drugs and will greatly broaden the application of peptides drugs.

Lipidation Based Molecule-Albumin Conjugation Service

In the past decade, much attention has been focused on lipidation that is emerging as a ponderable method for molecule-albumin conjugation due to its causative role in extending the half-life of drugs. With the accumulation of experience and the establishment of advanced half-life extension platforms, Creative Biolabs has a wealth of expertise in conjugating peptides and proteins with HAS and conjugating to albumin with peptide moiety to increase the half-life of the target molecule.

Creative Biolabs has always been professional in the half-life extension of drugs. Our excellent expert staff provides a variety of flexible and reliable strategies to meet the different purposes of your project, please contact us for more details.

References

1. Quinlan, G. J.; et al. Albumin: biochemical properties and therapeutic potential. Hepatology. 2005, 41(6): 1211-1219.
2. Bech, E. M.; et al. Chemical strategies for half-life extension of biopharmaceuticals: lipidation and its alternatives. ACS Medicinal Chemistry Letters. 2018, 9(7): 577-580.