Abstract

The understanding of gene regulation plays an important role in cancer therapy and epigenetics, which describe the molecular mechanisms by which environmental factors control the switching on and off of gene activities. One of the major mechanisms of epigenetic control is methylation and demethylation of lysine residues in histone proteins. The desire to understand the function of these modifications, promoted the development of artificial molecules that recognize and bind methyllysine. They are promising for a number of applications, e.g. as reagents in biochemical assays, in cell biology and to inhibit protein-protein interactions. Thereby, the discrimination of differently methylated lysines (monomethyl, dimethyl, trimethyl), both as a modified amino acid and in proteins, is of special interest.

One focus of the presentation is on a water-soluble macrocycle (1) and its ability to recognize differently methylated lysines. The results show that the host molecule discriminates lower methylated lysines, while higher methylated ones bind rather selectively. Binding studies were carried out with respectively methylated lysines using NMR spectroscopy and our findings have been analyzed by energy-minimization calculations. A second focus is on macrocycles with intrinsic fluorescence. We suggested the name ‘fluorescophane’ for such macrocyclic com-pounds. By inserting a condensed aromatic system, the resulting receptor is envisaged to enable better C−H···π and cation···π inter¬actions with the respective alkyl ammonium ion and at the same time allow an efficient quanti¬fication of host/guest interactions.