SPP 1623:  Chemoselective Reactions for the Synthesis and Application of Functional Proteins

• Subject Area: Chemistry ; Biology
• Term: from 2012 to 2021
• Website: Homepage
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 198742546

The Priority Programme focusses on the development of chemical methods for obtaining functional proteins. Thereby, the participating research groups aim to develop new approaches to tackle biological questions by combining chemoselective organic reactions with modern techniques from biochemistry and molecular biology. Within the funded projects of the Priority Programme several scientific aims will be addressed, for instance innovative chemoselective routes in protein synthesis for in vivo applications. Another central element is the support of collaborations between chemical and biological, biophysical or biochemical research groups, in particular for those focussing on proteins with homogeneous posttranslational modifications and/or biophysical probes, because these modified proteins cannot be accessed by standard molecular biology techniques. Important protein targets within the Priority Programme include intra- and extracellular proteins, for example glycoproteins, histones and proteins involved in signal transduction events. Furthermore, biomedical relevant proteins will be targeted for therapeutic and diagnostic applications, which will be of special relevance for the pharmaceutical and biotechnological industry.

• DFG Programme: Priority Programmes
• International Connection: Sweden

Projects

• Application of an enzymatic protein labeling strategy based on CDP-choline analogues (Applicant Itzen, Aymelt )
• Cellular Logistics - Traceless protein modification by small high-affinity tags in living cells (Applicant Tampé, Robert )
• Chemoselective DNA conjugation of proteins to study multienzyme clomplexes (Applicants Niemeyer, Christof M. ;  Schulz, Frank )
• Chemoselective Staudinger-induced Michael-additions to antibodies to analyze protein homeostasis in C. elegans (Applicants Hackenberger, Christian ;  Kirstein, Janine )
• Co- and post-translational engineering of the therapeutic protein Erythropoietin with non-natural amino acids (Applicant Rubini, Marina )
• Coordination Funds (Applicant Hackenberger, Christian )
• Establishing a Chemical Tool Box for Modified Nucleosomes and its Application for Analysis of the Histone Code (Applicants Fischle, Wolfgang ;  Schwarzer, Dirk )
• Establishing strategies for sortase-catalyzed multi-peptide assemblies to profile T-cell selectivity (Applicants Freund, Christian ;  Schwarzer, Dirk )
• Exploiting Diels-Alder Reactions with Inverse Electron Demand for Bioorthogonal Labeling of Alkene-Substituted Fucosylated Glycoproteins in Cells (Applicant Wittmann, Valentin )
• Genetic code expansion for protein-protein and protein-DNA interaction studies in dynamic cellular systems (Applicants Bultmann, Sebastian ;  Lang, Kathrin )
• Mechanistic studies of Legionella effector RavZ function in host autophagy using semi-synthetic LC3 proteins (Applicant Wu, Yaowen )
• New approaches for the site-selective chemical modification of therapeutic proteins under mild conditions (Applicant Mootz, Henning D. )
• New Methods for the Synthesis of glycosylphosphatidylinositol anchored proteins with therapeutic applications (Applicant Varón Silva, Daniel )
• Peptide-templated bioconjugation of proteins on and in live cells for studies of GPCR trafficking and crosstalk (Applicants Beck-Sickinger, Annette G. ;  Seitz, Oliver )
• Programmable and Chemoselective Protein-DNA Crosslinking for Sensitive Detection of 5-Formylcytosine (Applicant Summerer, Daniel )
• Protein labeling in living cells - A combination of enzyme mediated peptide labeling and inverse electron demand Diels-Alder cycloaddition (Applicant Wombacher, Richard )
• Reconstitution of tyrosine kinase signaling in cell-free systems: Synthetic membrane protein dimerization and lipid modification (Applicants Kubick, Stefan ;  Schiller, Stefan )
• Selective multifunctionalization of antibody fragments and antibodies by enzyme-mediated orthogonal ligations (Applicants Diederichsen, Ulf ;  Kolmar, Harald )
• Semisynthesis of antibody drug conjugates via biocatalysis (Applicant Bordusa, Frank )
• Semisynthesis of natural glycoforms of human erythropoietin (Applicant Unverzagt, Carlo )
• Site-specific functionalization of nanobodies: From labeling to cellular uptake (Applicants Cardoso, Maria Cristina ;  Hackenberger, Christian ;  Leonhardt, Heinrich )
• Specific labeling of proteins within living cells with single residue precision through genetically encoded click chemistry (Applicants Lemke, Edward A. ;  Schultz, Carsten )
• Targeted poly(ADP-ribosyl)ation of proteins (Gezielte Poly(ADP-Ribosyl)ierung von Proteinen) (Applicant Marx, Andreas )
• Twofold bio-orthogonal derivatization of antibody fragments by two different C(alpha)-formylglycine generating enzymes for generation of antibody-drug conjugates (Applicants Dierks, Thomas ;  Müller, Kristian ;  Sewald, Norbert )

• Spokesperson: Professor Dr. Christian Hackenberger