De Novo Protein Surface Design: Use of Cation-π Interactions to Enhance Binding between an α-Helical Peptide and a Cationic Molecule in 50 % Aqueous Solution

The relative position of the Asp and Trp residues in a peptide chain is important for recognizing a tetraguanidinium receptor through hydrogen bonding and cation–π interactions. The molecule not only binds with high affinity (Ka=1.1×108 M−1), it also stabilizes the helical conformation of the peptide (see schematic representation) as demonstrated by NMR and CD spectroscopy.