Four tripeptides corresponding to the C-terminal region of angiotensin II were synthesized. One of thesepeptides (Ac-His-Pro-Ile) showed moderate binding affinity for the AT2 receptor. Two aromatic histidine-related scaffolds were synthesized and introduced in the tripeptides to give eight new peptidomimeticstructures. Three of the new peptide-derived druglike molecules exhibited selective, nanomolar affinity forthe AT2 receptor. These ligands may become lead compounds in the future development of novel classes ofselective AT2 receptor agonists.
