Peptoid-peptide hybrids as potent novel melanocortin receptor ligands.
All possible peptoid-peptide hybrids of an MC4 receptor agonist were synthesized and investigated on cells expressing different melanocortin (MC) receptor subtypes and for rat grooming behavior. In general, receptor selectivity remained while affinity and potency were decreased. The length of the functional group of Trp was more important for MC3 and MC5 than for MC4 receptor binding. In general, the potency of the peptoid-peptide hybrids to increase rat excessive grooming behavior correlated well with MC4 receptor pharmacology.
Department of Medicinal Chemistry, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, P.O. Box 80082, 3508 TB Utrecht, The Netherlands.
John A W
JA
Kruijtzer
Wouter A J
WA
Nijenhuis
Nienke
N
Wanders
Willem Hendrik
WH
Gispen
Rob M J
RM
Liskamp
Roger A H
RA
Adan
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001665:Binding Sites; D007276:Injections, Intraventricular; D008024:Ligands; D009842:Oligopeptides / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D034444:Peptoids / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D044104:Receptor, Melanocortin, Type 3 / Q000378:metabolism; D044105:Receptor, Melanocortin, Type 4 / Q000378:metabolism*; D018043:Receptors, Corticotropin / Q000378:metabolism; D044101:Receptors, Melanocortin / Q000378:metabolism*
D008024:Ligands; D009842:Oligopeptides; D034444:Peptoids; D044104:Receptor, Melanocortin, Type 3; D044105:Receptor, Melanocortin, Type 4; D018043:Receptors, Corticotropin; D044101:Receptors, Melanocortin; C086971:melanocortin 5 receptor