title: Discovery of 1-amino-4-phenylcyclohexane-1-carboxylic acid and its influence on agonist selectivity between human melanocortin-4 and -1 receptors in linear pentapeptides.
abstract: Linear pentapeptides (Penta-cis-Apc-DPhe-Arg-Trp-Gly-NH2) containing 1-amino-4-phenylcyclohexane-1-carboxylic acid (cis-Apc) and substituted Apc are potent hMC4R agonists and they are inactive or weakly active in hMC1R, hMC3R, and hMC5R agonist assays. This study, together with our earlier report on 5-BrAtc, demonstrated the importance of replacing His6 with phenyl-containing rigid templates in achieving good hMC4R agonist potency and selectivity against hMC1R in linear pentapeptides.
authors.affiliation: Roche Research Center, Hoffmann-La Roche Inc., 340 Kingsland Street, Nutley, NJ 07110, USA. xin-jie.chu@roche.com
authors.forename: Xin-Jie
authors.initials: XJ
authors.lastname: Chu
authors.forename: David
authors.initials: D
authors.lastname: Bartkovitz
authors.forename: Waleed
authors.initials: W
authors.lastname: Danho
authors.forename: Joseph
authors.initials: J
authors.lastname: Swistok
authors.forename: Adrian Wai-Hing
authors.initials: AW
authors.lastname: Cheung
authors.forename: Grazyna
authors.initials: G
authors.lastname: Kurylko
authors.forename: Karen
authors.initials: K
authors.lastname: Rowan
authors.forename: Mitch
authors.initials: M
authors.lastname: Yeon
authors.forename: Lucia
authors.initials: L
authors.lastname: Franco
authors.forename: Lida
authors.initials: L
authors.lastname: Qi
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Keith
authors.initials: K
authors.lastname: Yagaloff
mesh_terms: D000595:Amino Acid Sequence; D002264:Carboxylic Acids / Q000737:chemistry* / Q000494:pharmacology*; D003510:Cyclohexanes / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D044102:Receptor, Melanocortin, Type 1 / Q000819:agonists*; D044105:Receptor, Melanocortin, Type 4 / Q000819:agonists*; D012680:Sensitivity and Specificity; D013379:Substrate Specificity
chemical_list: C506369:1-amino-4-phenylcyclohexane-1-carboxylic acid; D002264:Carboxylic Acids; D003510:Cyclohexanes; D044102:Receptor, Melanocortin, Type 1; D044105:Receptor, Melanocortin, Type 4