Synthesis of a novel potent cyclic peptide MC4-ligand by ring-closing metathesis.
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.
Wels
Bas
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Department of Medicinal Chemistry, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, PO Box 80082, 3508 TB Utrecht, The Netherlands.
Kruijtzer
John A W
JA
Garner
Keith
K
Nijenhuis
Wouter A J
WA
Gispen
Willem Hendrik
WH
Adan
Roger A H
RA
Liskamp
Rob M J
RM
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
D008024:Ligands; D010456:Peptides, Cyclic; D044105:Receptor, Melanocortin, Type 4; D009074:Melanocyte-Stimulating Hormones