For Research Use Only. Not for Clinical Use.

Brief Introduction of Lipidation Based Half-life Extension

Lipidation refers to the covalent combination of fatty acids and peptide side chains, which is one of the chemical modification methods to improve the half-life. The basic mechanism of its prolonging half-life is to reduce renal filtration by increasing hydrodynamic radius. Lipidation reduces the water solubility of the peptide but can be regulated by the connection between the peptide and the fatty acid. Changes in linker engineering and lipid moiety can affect self-aggregation and contribute to increased half-life by slowing biological distribution. Lipidation of various peptides has been explored, especially in diabetes.

Fig.1 Examples of lipid moieties used for half-life extension of biopharmaceuticals. (van Witteloostuijn, 2016)

Example of Site-Specific Lipidation of a Small-Sized Protein Binder

The researchers conjugated palmitic acid to 4-azido-L-phenylalanine on the repebody through copper-free click chemistry, the resulting repebody (Pal-Rb) was obtained. They investigated the pharmacokinetic profile of a palmitic acid-conjugated repebody (Pal-Rb) in mice. A palmitic acid conjugated in repebody showed a binding capacity for an MSA, extending the blood circulation time up to 10.7 h, whereas WT-Rb had a shorter half-life of 20 min. The prolonged blood half-life and enhanced bioavailability of the lipidated repebody led to a significant enhancement in tumor suppression in the xenograft mice model. These results show that the current method can be effective to elongate the circulation time in blood and increase the bioavailability of proteins with low molecular weight and therefore lead to enhancement of their therapeutic effect.

Fig.2 Site-specific lipidation of a human IL6-targeting repebody. (Kim, 2020)

Custom Services of Lipidation Based Half-Life Extension

Creative Biolabs offers customed solutions based on lipidation at every step in half-life extension drug development. Our team is backed by knowledgeable researchers and experienced technologists. Our customers need a partner who can deliver flexible and valuable solutions. That's what we do every day. If you are interested in our lipidation-based half-life extension services, please do not hesitate to contact us for more details.

References

1. van Witteloostuijn, S.B.; et al. Half-life extension of biopharmaceuticals using chemical methods: alternatives to PEGylation. ChemMedChem. 2016, 11(22): 2474-2495.
2. Kim, T.Y.; et al. Site-Specific Lipidation of a Small-Sized Protein Binder Enhances the Antitumor Activity through Extended Blood Half-Life. ACS omega. 2020, 5(31): 19778-19784.