The power of chemoselectivity: Functional protein-conjugates for intra- and extracellular targeting  — ASN Events
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The power of chemoselectivity: Functional protein-conjugates for intra- and extracellular targeting  (#68)

Christian Hackenberger 1
  1. FMP Berlin und HU Berlin, Berlin, Germany

Our lab aims to identify new bioorthogonal reactions for the synthesis and modification of functional peptides and proteins. We apply these highly selective organic reactions1 to study functional consequences of naturally occurring posttranslational protein modifications (PTMs), in particular phosphorylated Lys- and Cystein-peptides,2 as well as to generate novel peptide- and protein-conjugates for pharmaceutical and medicinal applications.

In this presentation, l will focus on the chemoselective modification of functional proteins. For protein modification we use a combined approach recently developed chemoselective reactions and enzymatic ligations, for instance the so-called P54 or Tub-tag labeling.5  Thereby, we generate new antibody-drug conjugates5 as well as cell-permeable antibodies to interfere with intracellular targets.6 

  1. D. Schumacher, C.P.R. Hackenberger, Curr. Opin. Chem. Biol. 2014, 22, 62-69.
  2. a) J. Bertran-Vicente, R.A. Serwa, M. Schümann, P. Schmieder, E. Krause, C.P.R. Hackenberger, J. Am Chem. Soc. 2014, 136(39), 13622-13628; b) J. Bertran-Vicente, M. Penkert, O. Nieto, M. Schümann, P. Schmieder, E. Krause, C.P.R. Hackenberger, Nature Comm. 2016, 7,12703.
  3. 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) A.F.L. Schneider, A.L.D. Wallabregue, L. Franz, C.P.R. Hackenberger, Bioconjugate Chem. 2019, 30, 400-404.
  4. a) M.-A. Kasper, et al., Angew. Chem. Int. Ed. 2019, doi:10.1002/anie.201814715; b) M.-A. Kasper, et al., Chem. Sci. 2019, 10, 6322-6329.
  5. 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
  6. M.-A. Kasper, et al., Angew. Chem. Int. Ed. 2019, doi:10.1002/anie.201904193