The power of chemoselectivity: Functional protein-conjugates for intra- and extracellular targeting

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

In this presentation l will focus on the chemical modification of functional proteins as well as their cellular delivery. Thereby, we employ cyclic cell penetrating peptides (cCPPs) to transport a functional full length protein to specific intracellular compartments of living cells as recently demonstrated by the direct delivery of different fluorescent proteins. For protein modification we use a combined approach of intein expression as well as recently developed chemoselective reactions and enzymatic ligations, for instance the so-called P5 or Tub-tag labeling. This concept is finally applied to generate new antibody-drug conjugates as well as cell-permeable nanobodies, i.e. small antigen binding proteins that remain active within the reductive milieu inside living cells, to interfere with intracellular targets.

Professor Christian P. R. Hackenberger

Christian P. R. Hackenberger completed his graduate studies in chemistry at the universities of Freiburg and UW Madison and his doctoral studies in 2003 at the RWTH Aachen. After a postdoctoral position at MIT with Barbara Imperiali, he started his own group at the Freie Universität Berlin in 2005. In 2012, he was appointed Leibniz-Humboldt Professor for Chemical Biology at the Leibniz-Research Institute for Molecular Pharmacology and the Humboldt Universität zu Berlin.

His group works on the development of new chemoselective and bioorthogonal reactions, the identification and analysis of novel PTMs, the engineering of protein-based pharmaceuticals and novel approaches to functional protein synthesis and delivery, in particular for the labeling and modification of different antibody formats. He is co-founder of the start-up 'Tubulis Technologies', which ventures into engineering better tolerable cancer drugs based on protein- and antibody-drug conjugates.

Seminar host: Dr Christina Schroeder