Patent ID: 7307063
Filing Date: 2007-12-11
Classification: A61K,A61P,C07K

Abstract:
1. A manufactured peptide or a pharmaceutically acceptable salt thereof with a metal ion-binding domain consisting of three contiguous amino acids forming an N 3 S 1 ligand and complexed to a metal ion and a determined biological-function domain, wherein the metal on-complexed peptide or salt thereof is an agonist increasing cAMP production in a functional cAMP assay and specific for at least one of melanocortin receptors MC-3 or MC-4, wherein at least a portion of said biological-function domain is co-extensive with at least a portion of said metal ion-binding domain, and wherein said biological-function domain is conformationally constrained upon complexing said metal ion-binding domain with a metal ion, the peptide being of any of the formulas: wherein R Aaa is an L- or D-configuration cationic amino acid with a positively charged side chain, including L-configuration Lys, Arg, Orn, Dpr or Dbu, and derivatives, analogs or homologs thereof, including both natural and synthetic amino acids, and further wherein Aaa provides an N (nitrogen atom) for metal ion complexation; Bbb is an L- or D-configuration amino acid with an aromatic side chain, including D-configuration Phe, Phe(4′-Cl), Phe(3′,4′-di-Cl), Phe(4′-NO Ccc is an amino acid that provides both an N, from the alpha amino group, and an S (sulfur atom), from a side chain group, for metal ion complexation, including L- or D-configuration Cys, Pen and Hcys; Lll is a D-configuration amino acid with an aromatic side chain, including D-configuration Phe, Phe(4′-Cl), Phe(3′,4′-diCl), Phe(4′-NO R Ddd is an amino acid that provides an S, from a side chain group, for metal ion complexation, including L- or D-configuration Cys, Pen and Hcys; R R Eee is an uncharged L- or D-configuration amino acid that provides an N for metal ion complexation, including Gly and L-configuration Ala, Nle, Leu, Val, Phe or Trp, and derivatives, analogs or homologs thereof, including both natural and synthetic amino acids, and wherein Eee is optionally an amino acid with an aliphatic side chain; Fff is an L- or D-configuration aromatic amino acid, including D-configuration Phe, Phe(4′-Cl), Phe(3′,4′-diCl), Phe(4′-NO Ggg is an L- or D-configuration aromatic amino acid, including L-configuration Phe, Phe(4′-Cl), Phe(3′,4′-diCl), Phe(4′-NO R Hhh is an L- or D-configuration cationic amino acid with a positively charged side chain, including L-configuration Lys, Arg, Orn, Dpr or Dbu, and derivatives, analogs or homologs thereof, including both natural and synthetic amino acids, wherein Hhh does not provide an N for metal ion complexation; Iii is an L- or D-configuration amino acid that provides an N for metal ion complexation, including Ala, Gly, Nle, Val, Leu, Ile, His, Lys, or Arg, and derivatives, analogs or homologs thereof, including both natural and synthetic amino acids; Jjj is an L- or D-configuration amino acid with an aromatic side chain, including D-configuration Phe, Phe(4′-Cl), Phe(3′,4′-diCl), Phe(4′-NO Kkk is an L- or D-configuration cationic amino acid with a positively charged side chain, including L-configuration Lys, Arg, Orn, Dpr or Dbu, and derivatives, analogs or homologs thereof, including both natural and synthetic amino acids, wherein Aaa does not provide an N for metal ion complexation.