Evaluation of the molecular interactions of fluorinated amino acids with native polypeptides


Christian Jaeckel, jaeckel@chemie.fu-berlin.de1, Mario Salwiczek, mario.salwiczek@web.de2, and Beate Koksch, koksch@chemie.fu-berlin.de2. (1) Organic Chemistry, Freie Universitšt Berlin, Takustr. 3, Berlin, 14195, Germany, (2) Department of Biology, Chemistry and Pharmacy; Institute of Chemistry and Biochemistry, Freie Universitšt Berlin, Takustr. 3, Berlin, 14195, Germany
The incorporation of fluorine into amino acids creates a new and exciting class of building blocks for peptide design and protein engineering. Properties of fluoroalkyl groups like space-filling and lipophilicity are still controversially discussed issues. A systematic study of the impact of a fluorination on the interaction profile of an amino acid within a native polypeptide environment is necessary to extend the application spectra of fluorinated building blocks to the rational design of peptide based drugs. We have developed a screening system for the fast and systematic investigation of the properties as well as the molecular interactions of fluoro-substituted amino acids with native polypeptides. This screening system is based on an α-helical coiled coil folding motif and could be shown to be sensitive enough to even detect differences of one fluorine atom in an amino acid side chain. First results gave already valuable new information about the interplay between space-filling and polarity of fluoroalkyl groups in respect to the influence on peptide/peptide interaction.