Synthesis of a new class of druglike angiotensin II C-terminal mimics with affinity for the AT(2) receptor

Department of Medicinal Chemistry, Division of Organic Pharmaceutical Chemistry, BMC, Uppsala University, P.O. Box 574, SE-751 23 Uppsala, Sweden.
Journal of Medicinal Chemistry (Impact Factor: 5.48). 05/2007; 50(7):1711-5. DOI: 10.1021/jm0613469
Source: PubMed

ABSTRACT Four tripeptides corresponding to the C-terminal region of angiotensin II were synthesized. One of these peptides (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 peptidomimetic structures. Three of the new peptide-derived druglike molecules exhibited selective, nanomolar affinity for the AT2 receptor. These ligands may become lead compounds in the future development of novel classes of selective AT2 receptor agonists.

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