Synthesis of a new class of druglike angiotensin II C-terminal mimics with affinity for the AT2 receptor.
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.
Georgsson
Jennie
J
Department of Medicinal Chemistry, Division of Organic Pharmaceutical Chemistry, BMC, Uppsala University, P.O. Box 574, SE-751 23 Uppsala, Sweden.
Sköld
Christian
C
Botros
Milad
M
Lindeberg
Gunnar
G
Nyberg
Fred
F
Karlén
Anders
A
Hallberg
Anders
A
Larhed
Mats
M
D000804:Angiotensin II / Q000737:chemistry*; D000818:Animals; D005260:Female; D066298:In Vitro Techniques; D008024:Ligands; D008099:Liver / Q000378:metabolism; D008958:Models, Molecular; D018716:Molecular Mimicry; D009215:Myometrium / Q000378:metabolism; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D044139:Receptor, Angiotensin, Type 2 / Q000819:agonists*; D013329:Structure-Activity Relationship; D013552:Swine
D008024:Ligands; D009842:Oligopeptides; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II