Distinguished iNANO Lecture: Functional protein- and antibody-conjugates for intra- and extracellular targeting

Professor Dr. Christian P. R. Hackenberger, Humboldt Universität zu Berlin and Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Berlin, Germany

Functional protein- and antibody-conjugates for intra- and extracellular targeting

In this presentation, l will focus on the chemical modification of functional proteins for for pharmaceutical and medicinal applications.¹ In my laboratory, we use a combined approach of recently developed chemoselective reactions and enzymatic ligations, for instance the so-called P5-² or Tub-tag³-labeling, for bioconjugation.

By generating stable antibody-drug conjugates (ADCs),^2b structurally defined multivalent scaffolds⁴ or cell-permeable antibodies via conjugating cyclic cell-penetrating peptides,⁵ we provide new modalities for most challenging pharmaceutical targets, including next generation cancer therapeutics or novel inhibitors against viral infections.

References

1. D. Schumacher, C.P.R. Hackenberger, Curr. Opin. Chem. Biol. 2014, 22, 62-69.
2. a) M.-A. Kasper et al., Angew. Chem. Int. Ed. 2019, 58, 11625-11630; b) M.-A. Kasper et al., Angew. Chem. Int. Ed. 2019, 58, 11631-11636; c) M.-A. Kasper et al., Chem Sci. 2019, 10, 6322-6329; d) C.E. Stieger, Angew. Chem. Int. Ed. 2021, 60, 15359-15364.
3. a) D. Schumacher, J. Helma, F.A. Mann, G. Pichler, F. Natale, E. Krause, M.C. Cardoso, C.P.R. Hackenberger, H. Leonhardt, Angew. Chem. Int. Ed. 2015, 54(46), 13787-13791, b) D. Schumacher, O. Lemke, J. Helma, L. Gerszonowicz, V. Waller, T. Stoschek, P.M. Durkin, N. Budisa, H. Leonhardt, B.G. Keller, C.P.R. Hackenberger, Chem. Sci. 2017, 8, 3471-3478.
4. D. Lauster, S. Klenk, …, S. Liese, A. Herrmann, C.P.R. Hackenberger, Nature Nanotech. 2020, 15, 373-379.
5. a) N. Nischan, H.D. Herce, F. Natale, N. Bohlke, N. Budisa, M.C. Cardoso, C.P.R. Hackenberger, Angew. Chem. Int. Ed. 2015, 54(6), 1950-1953; b) H. Herce, D. Schumacher, F.A. Mann, A. Ludwig, A. Schneider, M. Filies, S. Reinke, C. Cardoso, C.P.R. Hackenberger, Nature Chem. 2017, 9, 762-771; c) A.F.L. Schneider, A.L.D. Wallabregue, L. Franz, C.P.R. Hackenberger, Bioconjugate Chem. 2019, 30, 400-404; d) A.F.L. Schneider, M. Kithil, M.C. Cardoso, M. Lehmann, C.P.R. Hackenberger Nature Chem. 2021, 13, 530-539.
   
   Host: Professor Kurt V. Gothelf