Receptor properties of cyclic peptides composed of alternating natural amino acids and 3-aminobenzoic acid derivatives

Abstract

Our investigations into the receptor properties of cyclic hexapeptides composed of alternating natural amino acids and 3-aminobenzoic acids are presented. Peptides of this type bind cations such as quaternary ammonium ions by cation-π interactions with the aromatic subunits. Anions can be bound, but only when they are able to form hydrogen bonds to the peptide NH groups. Anion complexation causes a receptor preorganization and results in a drastic increase in cation complex stability. In the absence of anions that bind to the NH groups, the solution conformation and consequently also the receptor properties of the peptides are sensitive to the nature of the subunits from which they are composed. A cyclic peptide with proline subunits, e.g., forms more stable cation complexes than a more flexible peptide with glutamic acid subunits. Conformational control can alternatively be achieved by introducing substituents in the 4-position of the aromatic subunits of the proline containing peptide. By varying these substituents systematically, receptors are accessible whose cation complex stabilities range between ca. 100 and 10,000 M −1 in CDCl 3. Interestingly, substituents other than H completely eliminate the anion affinity of the corresponding macrocycles. Residues in the 5-position of the aromatic subunits have no influence on peptide conformation. They can be used as binding sites for guest molecules, and peptide derivatives carrying substituents with free carboxylate groups at the 5-position of the aromatic subunits bind monosaccharides in chloroform.