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bioRxiv · 10.1101/2020.07.24.219675

A twofold strategy for the protection of therapeutic peptides by attachment to the protease-resistant and fusogenic protein, saposin C

de Alba, E.·Sandin, S. I.·Randolph, C. J.
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Abstract

A great challenge of therapeutic peptides (biologics) is their short half-life. However, biologics can be protected by encapsulation in liposomes used as drug-delivery platforms. Liposomes are typically incorporated into cells by endocytic pathways, which eventually expose therapeutics to favorable proteolytic conditions. To enhance biologics protection, we report the design and characterization of a liposome-protein chimera combining the liposome fusogenic properties of peripheral-membrane protein saposin C, covalently linked to a proapoptotic peptide (the active domain of Bcl-2 protein PUMA). We show by NMR that the saposin C component of the chimera is capable of binding liposomes and that the peptide binds prosurvival Bcl-xL, thus following known PUMAs mechanism to induce cell death. These results indicate that the function of the individual components is preserved in the chimera. Our results point to a promising twofold strategy for drug delivery to; 1) avoid endocytosis by promoting liposome-membrane fusion, 2) provide additional protection by attachment to a stable, protease-resistant protein, which is a well-known method commonly used to prolong biologics half-life.

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de Alba, E., Sandin, S. I., Randolph, C. J.. 2020-07-25. A twofold strategy for the protection of therapeutic peptides by attachment to the protease-resistant and fusogenic protein, saposin C. https://doi.org/10.1101/2020.07.24.219675

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