This topic is devoted to the rational and combinatorial engineering of proteins with tailored properties as well as to the development of small molecules that interact with intracellular proteins in a specific manner in order to manipulate their biochemical functions (nowadays called chemical biology or chemical genetics).

1. In order to understand the function of proteins in living cells it is necessary to develop new chemical probes that specifically modulate protein function as inhibitors of single proteins or of protein-protein interactions. These small functional molecules will help to elucidate the biological role of proteins in cells and, possibly, to steer cellular behaviour and differentiation. Collaboration are planned between the synthetic groups and with groups working in the proteomics area C. In addition, methods are required that allow us to label proteins selectively within cells to track their localization, e.g., by single molecule spectroscopy (collaboration with area A). We need new non-toxic dyes that report membrane depolarization events fast and with a strong increase and shift of the fluorescence to boost measurements of neuronal activities in tissues into a new dimension.

2. In order to understand how protein expression is linked to disease states it is essential to perform quantitative analysis of protein function within cells and cell extracts. For this task, new chemical tools such as fluorescence- and biotin-labeled inhibitors of enzyme function are needed (functional protein profiling in cells) which can tag the proteins at question. Links exist already between the Sieber and the Mann group (area C).

3. A major goal of contemporary protein science is to make proteins that are difficult to handle more amenable to biochemical investigation via alteration of their amino acid sequence. The prime research focus in CIPSM will be the development of strategies to enhance the folding efficiency of recombinant proteins, including membrane proteins, to increase their solubility, and to optimize affinity tags, especially with respect to current efforts in structural proteome analysis. The entire consortium, in particular research area A, B and C will profit from methods such as the Strep-tag technique developed within this area.

4. The construction of proteins with improved or even novel properties is of considerable interest in biotechnology and medicine. A topical trend in this area is the engineering of artificial binding proteins that are based on alternative protein scaffolds, and which are expected to possess advantageous features compared with conventional antibodies, in particular for therapeutic applications (for example, with binding proteins directed against the Alzheimer -amyloid peptide, see research area F). Along these lines, future attempts to engineer novel enzymes appear promising for chemical technology, especially with regard to stability, catalytic activity, and substrate specificity.

Principal Investigators

• Thomas Carell, W3 Dept. Chemie und Biochemie, LMU

• Arne Skerra, W3 Biologische Chemie, TUM

• Designated successor of Prof. Bacher, W3, Biochemistry, TUM

• Dieter Langosch, W3 Chemie der Biopolymere, TUM

• Angelika Görg, AG Proteomik, TUM, to be succeeded by N.N. W3 Lst Bioanalytics, TUM

Associated Groups

• Thorsten Berg, Junior group, MPI Biochemie, Martinsried

• Paula Braun, Junior group, Botany, Biology Department I, LMU

• Nediljko Budisa, BioFuture Independent Research Group, MPI Biochemie, Martinsried

• Thomas Mayer, Junior group. MPI Biochemie, Martinsried

• Gunther Meister, Junior group, MPI Biochemie, Martinsried

• Stefan Sieber, Junior group, Organische Chemie, LMU

• Hans-Jürgen Wester/Markus Schwaiger, W2 Radiopharmazie/W3 Nuklearmedizin, TUM