Area B: Synthetic Proteins
Research Area B aims at the generation and application of synthetic proteins.
|B1||Carell||Designer E. colis’ for the manufacturing of chemically modified proteins for click modification|
|B2||Jung/Lassak||Synthetically modified variants of translation elongation factor P in vitro and in vivo|
|B3||Skerra||Expansion of the genetic code|
|B4||Schneider||Functionalized cyclic peptides|
|B5||Hoffmann-Roeder||Synthesis of functional bacterial flagellin glycoprotein mimics|
The Carell group develops new chemical methods to specifically modify biomolecules. They develop new phosphoramidite building blocks for the incorporation of epigenetic bases into DNA and they develop click-chemistry based tools to insert unnatural amino acids into proteins. The final target compounds are chemically and structurally more diverse biomolecules that go beyond the biologically existing limitations.
Translation elongation factor P (EF-P) alleviates ribosome stalling at polyproline stretches. Activity of EF-P depends on post-translational modification of a conserved positively charged residue. Using an amber suppression system, we aim to replace the natural modification pathway by introducing artificial amino acids in order to modulate EF-P activity and thus promote or inhibt synthesis of polyproline containing proteins.
In parallel we will evolve the natural EF-P rhamnosyltransferase EarP with respect to substrate and sequence specificity, which finally will allow us to glycosylate any protein of choice.
The introduction of non-canonical amino acids into (bio)-synthetic proteins has been a long-standing effort in protein chemistry. We exploit the suppressor-mediated co-translational incorporation of artificial amino acids with new side chain functionalities at defined sites into recombinant proteins in order to create novel biomolecular reagents for biophysical, structural or biochemical research as well as biotechnological and pharmaceutical applications.
We are interested in the functionalization of genetically encoded cyclic peptide libraries and their application as selective inhibitors.
Protein glycosylation is of significant importance for a multitude of cellular recognition processes, including cell-cell interactions, and the immune response. For instance, in Campylobacter jejuni, the most frequent causative agent of bacterial gastroenteritis worldwide, glycosylation of the major flagellum glycoprotein flagellin A is closely related to virulence, adherence and filament stability. However, despite the importance of accurate glycosylation, precise structure-activity relationships with regard to the sites and structure of the glycans (i.e., minimal functional glycan composition), as well as their preferred binding partners, have not been conducted to date. To close this gap, we will prepare various functional units (modules) of flagellin glycoproteins of different sizes and with systematically varied glycosylation patterns based on pseudaminic acid (Pse) and legionaminic acid (Leg) derivatives (including chemically modified analogs). The resulting FlaA glycoprotein modules will be used for the development of diagnostic devices and vaccines, as well as for the elucidation of structure-function relationships with regard to glycan-mediated host-pathogen interactions.