Abstract

The design and synthesis of complex molecular scaffolds with defined physico-chemical properties present central challenges in current chemical research. The resulting molecules can provide access to novel therapeutics, catalysts and materials. For such agents, it is often essential to adopt defined three-dimensional structures, in which the degree of flexibility can preferably be adjusted in a controllable manner. The folding properties of peptides and proteins, usually determined by unique hydrogen bond patterns, provide an excellent basis for the design of molecules with tailored structural properties.^ABST[1] In our group, we use peptide and protein structures and combine those with non-natural small molecular scaffolds focusing on the synthesis of peptide-derived bioactive agents and the chemical engineering of proteins. Research highlights involve the structure-based design of bioactive peptidomimetics^[2,3] and the semi-synthesis of modified enzymes with enhanced activities.^[4] In addition, peptide-based molecular switches have been devised that respond to receptor binding and facilitate a homogeneous readout of this interaction in real-time.^[5]

[1] M. Pelay-Gimeno, A. Glas, O. Koch, T.N. Grossmann, Angew. Chem. Int. Ed., 2015, 54, 8896.

[2] A. Glas, D. Bier, G. Hahne, C. Rademacher, C. Ottmann, T.N. Grossmann, Angew. Chem. Int. Ed., 2014, 53, 2489.

[3] P.M. Cromm, S. Schaubach, J. Spiegel, A. Fürstner, T.N. Grossmann, H. Waldmann, Nature Commun., 2016, 7, 11300.

[4] M. Pelay-Gimeno, T. Bange, S. Hennig, T.N. Grossmann, Angew. Chem. Int. Ed., 2018, 57, 11164.

[5] C. Mueller, T.N. Grossmann, Angew. Chem. Int. Ed., 2018, 57, 17079.