title: Clinically validated peptides as templates for de novo peptidomimetic drug design at G-protein-coupled receptors.
abstract: Recent advances in the development of potent and selective peptide and non-peptide ligands for peptidergic receptors are anticipated to help further unravel the roles of class I and II G-protein-coupled receptors in the pathogenesis of human diseases and to accelerate the clinical utility of small molecule peptidomimetics. Peptidomimetic drug discovery directed towards somatostatin agonists, urotensin II antagonists, gonadotropin-releasing hormone antagonists, neurotensin and complement C5a modulators, melanocortin-4 agonists and vasopressin V(2) agonists has achieved success through integration of conformational-based drug design, site-directed mutagenesis, screening, combinatorial chemistry and classical medicinal chemistry. Acceptance that discreet ensembles of secondary structural motifs underpin the interactions of peptides with their cognate receptors has enabled the development of molecules which mimic or stabilize such pharmacophores.
authors.affiliation: Department of Medicinal Chemistry, Arena Pharmaceuticals, 6166 Nancy Ridge Drive, San Diego, CA 92121, USA. rjones@arenapharm.com
authors.forename: Robert M
authors.initials: RM
authors.lastname: Jones
authors.forename: P Douglas
authors.initials: PD
authors.lastname: Boatman
authors.forename: Graeme
authors.initials: G
authors.lastname: Semple
authors.forename: Young-Jun
authors.initials: YJ
authors.lastname: Shin
authors.forename: Susan Y
authors.initials: SY
authors.lastname: Tamura
mesh_terms: D015936:Complement C5a / Q000037:antagonists & inhibitors / Q000737:chemistry; D015195:Drug Design; D005934:Glucagon / Q000819:agonists / Q000737:chemistry; D052216:Glucagon-Like Peptide 1; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000737:chemistry; D009496:Neurotensin / Q000819:agonists / Q000737:chemistry; D010446:Peptide Fragments / Q000819:agonists / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*; D011498:Protein Precursors / Q000819:agonists / Q000737:chemistry; D044105:Receptor, Melanocortin, Type 4 / Q000819:agonists / Q000737:chemistry; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry*; D017483:Receptors, Vasopressin / Q000819:agonists / Q000737:chemistry; D013004:Somatostatin / Q000819:agonists / Q000737:chemistry; D014579:Urotensins / Q000037:antagonists & inhibitors / Q000737:chemistry
chemical_list: D010446:Peptide Fragments; D010455:Peptides; D011498:Protein Precursors; D044105:Receptor, Melanocortin, Type 4; D043562:Receptors, G-Protein-Coupled; D017483:Receptors, Vasopressin; D014579:Urotensins; D007987:Gonadotropin-Releasing Hormone; D009496:Neurotensin; D013004:Somatostatin; D015936:Complement C5a; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; C029677:urotensin II