title: Design of novel melanocortin receptor ligands: multiple receptors, complex pharmacology, the challenge.
abstract: The major pharmacophore for the melanocortin 1, 3, 4 and 5 receptors is the sequence -His-Phe-Arg-Trp-. There is a need for potent, biologically stable, receptor selective ligands, both agonists and antagonists, for these receptors. In this report we briefly examine the structural and biophysical approaches we have taken to develop selective agonist and antagonist ligands that can cross (or not) the blood brain barrier. Remaining questions and unmet needs are also discussed.
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, USA. hruby@u.arizona.edu
authors.forename: Victor J
authors.initials: VJ
authors.lastname: Hruby
authors.forename: Minying
authors.initials: M
authors.lastname: Cai
authors.forename: James
authors.initials: J
authors.lastname: Cain
authors.forename: Joel
authors.initials: J
authors.lastname: Nyberg
authors.forename: Dev
authors.initials: D
authors.lastname: Trivedi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015195:Drug Design; D057809:HEK293 Cells; D006801:Humans; D008024:Ligands; D008969:Molecular Sequence Data; D044101:Receptors, Melanocortin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054852:Small Molecule Libraries / Q000378:metabolism / Q000494:pharmacology; D013379:Substrate Specificity; D000521:alpha-MSH / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology
chemical_list: D008024:Ligands; D044101:Receptors, Melanocortin; D054852:Small Molecule Libraries; D000521:alpha-MSH