ORGN 199

Efficient receptors for peptides are needed to better understand biological processes in which peptide/peptide interactions are involved or for potential applications such as the development of chemosensors or molecular probes to interfere with these biological events.

The binding of small oligopeptides by artificial receptors under physiological conditions (= in water) still remains a challenging task due to the strong dependence of electrostatic interactions. Therefore, so far all artificial peptide receptors reported in the literature need additional hydrophobic, aromatic and/or metal-ligand interactions to achieve strong substrate complexation in water. Recently, we demonstrated that a tris-cationic receptor efficiently binds the tetrapeptide D-Glu-L-Lys-D-Ala-D-Ala-OH with high affinity in buffered water. This polar tetrapeptide is interesting due to its resemblance to a bacterial peptido­glycan which plays a crucial role in cell wall synthesis and antibiotic activity.

An inverse screening of this receptor against a tetrapeptide library revealed that the fully flexible peptide receptor shows not only significant substrate selectivity but also a remarkable sequence dependent stereoselectivity in the binding of polar tetrapeptides in water. This is a significant step forward on the way to a construction kit for artificial peptide receptors and therefore a possible important contribution for modern drug discovery.