Diederichsen/Kolmar

Selective multifunctionalization of antibody fragments and antibodies by enzyme-mediated orthogonal ligations

Since decades antibodies are invaluable tools for various applications mainly for use in diagnostics and therapy. They are target-specific and effective, stable and can be produced in large amounts. All antibodies are composed of two functional regions, namely the Fab and the Fc region. The Fab region is required for antigen recognition, while the Fc region couples the antibody to secondary immune effector functions. In the proposed project, the full length antibody as well as the antibody Fc region will be used as a scaffold for the display of bioactive molecules.

The main objective is to apply bioorthogonal chemical and enzyme-mediated ligation strategies that allow for selective endowment of antibodies with different ligands to site-specifically introduce cell recognition modules, toxic payloads, or compounds that mediate the release of bioactive molecules into the cytosol of a target cell. Multiple functionalization of antibodies and antibody fragments inherits a plethora of potential future applications in cell biology, biotechnology, and medicine.

Prof. Dr. Ulf Diederichsen
Georg-August-Universität Göttingen

Tel.: +49 551 39 33221
Fax: +49 551 39 22944

Email Prof. Diederichsen

Prof. Harald Kolmar
Technische Universität Darmstadt

Tel.: +49 6151 16 - 4742

Email Prof. Kolmar

Publications within the SPP 1623 project

S. Middel, C.H. Panse, S. Nawratil, U. Diederichsen
Chem. Bio. Chem.
2017, 18(23), 2328-2332
Native Chemical Ligation Directed by Photocleavable Peptide Nucleic Acid (PNA) Templates
Link to the article

V. Siegmund. B. Piater, B. Zakeri, T. Eichhorn, F. Fischer, C. Deutsch, S. Becker, L. Toleikis, B. Hock, U. Betz, H. Kolmar
Sci. rep.
2016, 6, 39291
Spontaneous Isopeptide Bond Formation as a Powerful Tool for Engineering Site-Specific Antibody-Drug Conjugates
Link to the article

B. Valldorf, H. Fittler, L. Deweid, A. Ebenig, S. Dickgiesser, C. Sellmann, J. Becker, S. Zielonka, M. Empting, O. Avrutina, H. Kolmar
Angew. Chem. Int. Ed.
2016, DOI: 10.1002/anie.201511894
An Apoptosis-Inducing Peptidic Heptad That Efficiently Clusters Death Receptor 5.
Link to the article

V. Siegmund, S. Schmelz, S. dickgiesser, J. Beck, A. Ebenig, H. Fittler, H. Frauendorf, B. Piater, U.A.K. Betz, O. Avrutina, A. Scrima, H.-L. Fuchsbauer, H. Kolmar
Angew. Chem. Int. Ed.
2015, 54, 13420-13424
Locked by Design: A Conformationally Constrained Transglutaminase Tag Enables Efficient Site-Specific Conjugation
Link to the article

S. Dickgiesser, N. Rasche, D. Nasu, S. Middel, S. Hörner, O. Avrutina, U. Diederichsen, H. Kolmar
ACS Chem-Biol.
2015, 10(9), 2158-2165
Self-Assembled Hybrid Aptamer-Fc Conjugates for Targeted Delivery: A Modular Chemoenzymatic Approach
Link to the article

S. Hörner, C. Uth, O. Avrutina, H. Frauendorf, M. Wiessler, H. Kolmar
Chem. Commun.
2015, 51, 11130
Combination of inverse electron-demand Diels-Alder reaction with highly efficient oxime ligation expands the toolbox of site-selective peptide conjugations
Link to the article

F. Maass, J. Wüstehube-Lausch, S. Dickgießer, B. Valldorf, M. reinwarth, H.-U. Schmoldt, M. Daneschdar, O. Avrutina, U. Sahin, H. Kolmar
J. Pept. Sci.
2015, 8, 651-660
Cystine-knot peptides targeting cancer-relevant human cytotoxic T lymphocyte-associated antigen 4 (CTLA-4)
Link to the article

C. Nadler, A. Nadler, C. Hansen, U. Diederichsen
Eur. J. Org. Chem.
2015, 14, 3095-3102.
A novel photocleavable auxiliary for Extended Native Chemical Ligation
Link to the article

H. Fittler, O. Avrutina, M. Empting, H. Kolmar
J Pept sci. 2014, 20(6), 415-420
Potent inhibitors of human matriptase-I based on the scaffold of sunflower trypsin inhibitor.
Link to the article

B. Glotzbach, M. Reinwarth, N. Weber, S. Fabritz, M. Tomaszowski, H. Fittler, A. Christmann, O. Avrutina, H. Kolmar
PLoS One 2013, 8(10):e76956. DOI: 10.1371/journal.pone.0076956
Combinatorial optimization of cystine-knot peptides towards high-affinity inhibitors of human matriptase-1.
Link zum Artikel

B. Glotzbach, S. Schmelz, M. Reinwarth, A. Christmann, D.W. Heinz, H. Kolmar
Acta Crystallogr D Biol Crystalogr 2013, 69(Pt 1):114-20. DOI: 10.1107/S0907444912043880
Structural characterization of Spinacia oleracea trypsin inhibitor III (SOTI-III)
Link zum Artikel