| Autor: |
Singh A; 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., Tala SR; Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota , Minneapolis, Minnesota 55455, United States., Flores V; Department of Pharmacodynamics, College of Pharmacy, University of Florida , Gainesville, Florida 32610, United States., Freeman K; Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota , Minneapolis, Minnesota 55455, United States., Haskell-Luevano C; 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. |
| Abstrakt: |
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. |
