Chemical Protein Engineering
The research group led by Amelie Eriksson Karlström uses chemical protein engineering to generate new biomolecules with improved properties for diagnostic and therapeutic applications. Chemical modifications and semi-synthetic strategies are used to increase the thermal and proteolytic stability or to improve the biodistribution properties of proteins.
The group has expertise in protein engineering, peptide synthesis and bioconjugation chemistry. Recent efforts have been focused on site-specific antibody labeling and conjugation of affinity proteins to reporter groups such as DNA, peptide nucleic acid (PNA), photoswitchable probes, and fluorophores. The engineered affinity proteins are used for the development of new therapeutic strategies as well as new technologies for protein profiling of single cells and small extracellular vesicles.
An ongoing project explores a pretargeting strategy aiming to reduce the side effects and increase the efficacy of targeted radionuclide therapy of cancer. The method is based on using a PNA-conjugated tumor-targeting protein in combination with a radiolabeled, complementary PNA detection probe, to achieve high tumor uptake and low uptake in non-tumor organs.
Principal Investigator
Staff
Kristina Westerlund (Researcher)
Jacob Clinton (PhD student)
Master's Thesis projects
If you are interested in doing a Master's Thesis project in the group, please contact Amelie at ameliek@kth.se .
Selected recent publications
- Nagy, A., Ulmert, D., Zedan, W., Storey, C. M., Park, J. Geres, S., Lückerath, K., Sjöström, K., Westin, H., Peekhaus, N., Thorek, D. L. J., Eriksson Karlström, A. & Altai, M. (2024) “Impact of site-specific conjugation strategies on the pharmacokinetics of antibody conjugated radiotherapeutics”, Eur. J. Med. Chem., in press.
- Westerlund, K., Oroujeni, M., Gestin, M., Clinton, J., Rosly, A. H., Tano, H., Vorobyeva, A., Orlova, A., Eriksson Karlström, A. & Tolmachev, V. (2024) “Shorter peptide nucleic acid probes improve affibody-mediated peptide nucleic acid-based pretargeting”, ACS Pharmacol. Transl. Sci., 7, 1595-1611.
- Oroujeni, M., Tano, H., Vorobyeva, A., Liu, Y., Vorontsova, O., Xu, T., Westerlund, K., Orlova, A., Tolmachev, V. & Eriksson Karlström, A. (2022) ”Affibody-mediated PNA-based pretargeted co-treatment improves survival of trastuzumab-treated mice bearing HER2-expressing xenografts”, J. Nucl. Med., 63, 1046.
- Banijamali, M., Höjer, P., Nagy, A., Hååg, P., Paz Gomero, E., Stiller, C., Kaminskyy, V. O., Ekman, S., Lewensohn, R., Eriksson Karlström, A., Viktorsson, K. & Ahmadian, A. (2022) “Characterizing single extracellular vesicles by droplet barcode sequencing for protein analysis”, J. Extracell. Vesicles, 11, 12277.
- Stiller, C., Viktorsson, V., Paz Gomero, E., Hååg, P., Arapi, V., Kaminskyy, V. O., Kamali, C., De Petris, L., Ekman, S., Lewensohn, R. & Eriksson Karlström, A. (2021) “Detection of tumor-associated membrane receptors on extracellular vesicles from non-small cell lung cancer patients via immuno-PCR”, Cancers, 13, 922.
- Myrhammar, A., Rosik, D. & Eriksson Karlström, A. (2020) ”Photo-controlled reversible binding between the protein A-derived Z domain and immunoglobulin G”, Bioconjug. Chem., 31, 622-630.
- Stiller, C., Aghelpasand, H., Frick, T., Westerlund K., Ahmadian, A. & Eriksson Karlström, A. (2019) “Fast and efficient Fc-specific photoaffinity labelling to produce antibody-DNA-conjugates”, Bioconjug. Chem., 30, 2790-2798.
Dissertations from the group
Ábel Nagy (2024): Thesis title: "Bioconjugation of antibodies and affinity proteins for the development of novel diagnostic and therapeutic tools".
Hanna Tano (2022): Thesis title: "PNA and affinity protein tools for selective tumor targeting of radiopharmaceuticals".
Anders Myrhammar (2020): Thesis title: "Investigations of chemical and enzymatic functionalization of affinity proteins".
Anna Perols (2014): Thesis title: "Site-specific labelling of affinity molecules for in vitro and in vivo studies".
Joel Lindgren (2014) Thesis title: "Chemical engineering of small affinity proteins".
Nima Jokilaakso (2013) Thesis title: "A biotechnology perspective on silicon nanowire FETs for biosensor applications".
Daniel Rosik (2013) Thesis title: “On the design of affibody molecules for radiolabeling and in vivo molecular imaging”.
Torun Ekblad (2008) Thesis title: ”Chemical synthesis of affibody molecules for protein detection and molecular imaging”.
Björn Renberg (2006) Thesis title: ”Fluorescence-based ligand assays for protein detection using affibody affinity proteins”.