title: Synthesis and Pharmacology of α/β(3)-Peptides Based on the Melanocortin Agonist Ac-His-dPhe-Arg-Trp-NH2 Sequence.
abstract: The melanocortin-3 and -4 receptors are expressed in the brain and play key roles in regulating feeding behavior, metabolism, and energy homeostasis. In the present study, incorporation of β(3)-amino acids into a melanocortin tetrapeptide template was investigated. Four linear α/β(3)-hybrid tetrapeptides were designed with the modifications at the Phe, Arg, and Trp residues in the agonist sequence Ac-His-dPhe-Arg-Trp-NH2. The most potent mouse melanocortin-4 receptor (mMC4R) agonist, Ac-His-dPhe-Arg-β(3)hTrp-NH2 (8) showed 35-fold selectivity versus the mMC3R. The study presented here has identified a new template with heterogeneous backbone for designing potent and selective melanocortin receptor ligands.
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota , Minneapolis, Minnesota 55455, United States ; Department of Pharmacodynamics, College of Pharmacy, University of Florida , Gainesville, Florida 32610, United States.
authors.forename: Anamika
authors.initials: A
authors.lastname: Singh
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota , Minneapolis, Minnesota 55455, United States.
authors.forename: Srinivasa R
authors.initials: SR
authors.lastname: Tala
authors.affiliation: Department of Pharmacodynamics, College of Pharmacy, University of Florida , Gainesville, Florida 32610, United States.
authors.forename: Viktor
authors.initials: V
authors.lastname: Flores
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota , Minneapolis, Minnesota 55455, United States.
authors.forename: Katie
authors.initials: K
authors.lastname: Freeman
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota , Minneapolis, Minnesota 55455, United States ; Department of Pharmacodynamics, College of Pharmacy, University of Florida , Gainesville, Florida 32610, United States.
authors.forename: Carrie
authors.initials: C
authors.lastname: Haskell-Luevano
keywords: peptidomimetics; α/β3-peptides; β-amino acids