Fluorinated amino acids: Modulating the metabolic stability and self-assembly properties of peptides and proteins

FLUO 21

Mario Salwiczek, mario.salwiczek@web.de, Toni Vagt, vagt@chemie.fu-berlin.de, Matthias Hakelberg, mhb@chemie.fu-berlin.de, and Beate Koksch, koksch@chemie.fu-berlin.de. Department of Biology, Chemistry and Pharmacy; Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustr. 3, Berlin, 14195, Germany
Improving the biological and pharmaceutical properties of drug candidates by site-specific structural modifications is one of the main goals in medicinal chemistry. In this context the introduction of fluorine has proven to be one of the most successful concepts. Our research focuses on the development of appropriate peptide based model systems, which provide the ability to study the properties of fluorine as an amino acid side chain function in native protein environments. Using these model peptides we investigate the proteolytic stability of fluorine substituted peptides and are able to interpret the results in terms of non-covalent interactions of those peptides with enzymes. Another model system serves as a tool to study the effects of fluorine on the kinetics and thermodynamics of peptide self assembly applying SPR. With the help of this system we screen for preferred native binding partners of fluorinated amino acids using phage display.