title: Preparation of human Melanocortin-4 receptor agonist libraries: linear peptides X-Y-DPhe7-Arg8-Trp(or 2-Nal)9-Z-NH2.
abstract: Two libraries of hMC4R agonists, X-Y-DPhe(7)-Arg(8)-2-Nal(9)-Z-NH(2) and X-Y-DPhe(7)-Arg(8)-Trp(9)-Z-NH(2), totaling 185 peptides were prepared using Irori radiofrequency tagging technology and Argonaut Quest 210 Synthesizer, where X stands for N-caps, Y for His(6) surrogates and Z for Gly(10) surrogates. As a result of this study, His-modified pentapeptides with Trp were found to be more hMC4R potent than the corresponding 2-Nal analogs, novel N-caps and Gly surrogates were identified and 19 new peptides which are potent hMC4R agonists (EC(50) 1-15nM) and selective against hMC1R were discovered.
authors.affiliation: Roche Research Center, Hoffmann-La Roche Inc., Nutley, NJ 07110, USA. adrian.cheung@roche.com
authors.forename: Adrian Wai-Hing
authors.initials: AW
authors.lastname: Cheung
authors.forename: Lida
authors.initials: L
authors.lastname: Qi
authors.forename: Vijay
authors.initials: V
authors.lastname: Gore
authors.forename: Xin-Jie
authors.initials: XJ
authors.lastname: Chu
authors.forename: David
authors.initials: D
authors.lastname: Bartkovitz
authors.forename: Grazyna
authors.initials: G
authors.lastname: Kurylko
authors.forename: Joseph
authors.initials: J
authors.lastname: Swistok
authors.forename: Waleed
authors.initials: W
authors.lastname: Danho
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Keith
authors.initials: K
authors.lastname: Yagaloff
mesh_terms: D000595:Amino Acid Sequence; D005998:Glycine; D006801:Humans; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D019151:Peptide Library; D044105:Receptor, Melanocortin, Type 4 / Q000819:agonists*; D013329:Structure-Activity Relationship
chemical_list: D009842:Oligopeptides; D019151:Peptide Library; D044105:Receptor, Melanocortin, Type 4; D005998:Glycine