Technological platform for the development of novel and superior protein therapeutics based on precise chemical modification.
Our technological platform (s-EPL, streamlined Expressed Protein Ligation) is based on the use of engineered UltraFast split inteins for the site-specific modification of proteins. This strategy provides fast access to homogenous, site-specifically modified proteins.
- Site-specifically modified proteins can be generated with an absolute control of the identity of the modification as well as its location. The production of homogenous proteins with defined chemical structure is a highly desirable property as it simplifies analytical characterization of the product and regulatory development.
- Fully native modified proteins
Fully native site-specifically modified proteins can be obtained using s-EPL, eliminating the risk that the modification process damages the properties of the target protein. s-EPL does not require the incorporation of unnatural amino acids nor unnatural side chains on the antibody or protein to be labeled. It also does not require the alteration of pre-existing modifications, such as glycosylations or disulfides.
- s-EPL is compatible with different linker chemistries
s-EPL incorporates the desired modification (including linkers) via the formation of native, stable peptide bonds. This allows the release of the cargo to be fully controlled by the linker of choice, depending on the desired application or therapeutic goal.
- Several payloads at precisely controlled locations and stoichiometry
s-EPL allows the incorporation of not only one but several modifications into the target protein. Importantly, its orthogonality to other conjugation technologies allows incorporating different cargoes to the target protein, opening the door to new therapeutic opportunities.
- The proven versatility of Protein Ligation
s-EPL builds on the solid foundation established by Protein Ligation chemistries, which have been widely applied to the modification of almost any class of proteins. s-EPL is compatible with the modification of proteins produced by eukaryotic (including mammalian cell lines) or prokaryotic cells. Importantly, s-EPL does not not require the coexpression of additional enzymes or cofactors neither the reengineering of the protein synthesis machinery of the expressing cell line.
The potential of s-EPL has been demonstrated on a variety of protein targets including antibodies, hormones, signal transduction proteins, DNA binding proteins and enzymes.
- Hormones: leptin as PET imaging agent used to monitor hormone localization in mice and monkeys
- Signal transduction: Smad as photocross-linkers reporter for imaging of protein sub-localization in cells
- Ion channels: Kcsa for structural and biophysical studies to characterize ion channel function