title: Synthesis of a novel potent cyclic peptide MC4-ligand by ring-closing metathesis.
abstract: The synthesis of a novel potent cyclic peptide MC4-ligand by ring-closing metathesis (RCM) is described. Based on the Ac-Nle-Gly-Lys-D-Phe-Arg-Trp-Gly-NH2-MC4 ligand, Ac-Nle-Alg-Lys-D-Phe-Arg-Trp-Alg-NH2 was designed and synthesized followed by cyclization using RCM. Both compounds are high affinity and selective MC4-R-agonists. The cyclic RCM-peptide was more potent in a rat-grooming assay.
authors.affiliation: Department of Medicinal Chemistry, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, PO Box 80082, 3508 TB Utrecht, The Netherlands.
authors.forename: Bas
authors.initials: B
authors.lastname: Wels
authors.forename: John A W
authors.initials: JA
authors.lastname: Kruijtzer
authors.forename: Keith
authors.initials: K
authors.lastname: Garner
authors.forename: Wouter A J
authors.initials: WA
authors.lastname: Nijenhuis
authors.forename: Willem Hendrik
authors.initials: WH
authors.lastname: Gispen
authors.forename: Roger A H
authors.initials: RA
authors.lastname: Adan
authors.forename: Rob M J
authors.initials: RM
authors.lastname: Liskamp
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003500:Cyclization; D006801:Humans; D007668:Kidney / Q000187:drug effects; D008024:Ligands; D009074:Melanocyte-Stimulating Hormones / Q000737:chemistry / Q000378:metabolism; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000378:metabolism*; D051381:Rats; D044105:Receptor, Melanocortin, Type 4 / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D010456:Peptides, Cyclic; D044105:Receptor, Melanocortin, Type 4; D009074:Melanocyte-Stimulating Hormones