Guest Chemistry Lecture: Prof. Dr. Beate Koksch

Guest Chemistry Lecture by:
 

Prof. Dr. Beate Koksch  from  Freie Universität Berlin, Institute of Chemistry and Biochemistry, Takustr. 3, 14195 Berlin, Germany

with title:
Fluorinated amino acids in peptide and protein engineering

Abstract:

The ways in which fluorinated amino acids influence protein stability and function, as well as peptide-protein interactions are not easily generalized and, thus, a rational design applying fluorinated amino acids in peptide and protein engineering is currently not possible. [1] Our group has established a research program that aims at understanding the impact of fluorination in the context of protein environments. 
In course of our program we identified several key aspects which come along with the introduction of fluorine into peptides and proteins, as for example fluorine’s impact on proteolytic stability [2], the increase in polarity of otherwise hydrophobic amino acids [3], and changes in the structural propensity of amino acids and folding properties of peptides, respectively. [4] This talk will cover several aspects of our current efforts.   Recently, we found an indication for the formation of fluorine-water-networks between fluorine-bearing BPTI-analogues and residues of the binding pocket of trypsin. The formation of this fluorine-water-network was responsible not only for the restoration of the inhibitory activity of modified BPTI but also induced a specificity of BPTI analogs for some of the studied enzymes. [5]
In our actual study, we focus on the proofreading activity of amino acid-tRNA-synthetases and found a so far undescribed editing function of one such enzyme that is most likely induced by an interaction between the enzyme and the trifluoromethyl group of trifluoroethyl glycine (TfeGly). [6]
These results impressively show that the introduction of fluorine creates a new class of amino acids with a repertoire of functionalities that is unique to the world of proteins and orthogonal to the set of canonical amino acids.

[1] M. Salwiczek, et al. Chem.Soc.Rev. 2012, 41, 2135.
[2] V. Asante, J. Mortier, G. Wolber, B. Koksch^. Amino Acids 2014, 46 (12), 2733.
[3] M. Salwiczek, et al. Chem. Eur. J., 2009, 15 (31) 7628.
[4] U.I.M. Gerling, et al. Chem. Sci. 2014, 5 (2), 819.
[5] S. Ye, B. Loll, A.A. Berger, U. Mülow, C. Alings, M. Wahl, B. Koksch. Chem.Sci. 2015, 6, 5246.
[6] J. Völler, M. Dulic, U. Gerling-Driessen, H. Biava, T. Baumann, N. Budisa, I. Gruic-Sovuli, B. Koksch. ACS Central Science, 2017, 3 (1), 73–80

Further information / Host:

Prof. Dr. Gerd-Volker Röschenthaler, Professor of Chemistry (Focus Area Health, Life Sciences & Chemistry) - Tel: +49 421 200-3238, - Email:  g.roeschenthaler@jacobs-university.de - Link to homepage: http://groeschent.user.jacobs-university.de