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.
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.
Chu
Xin-Jie
XJ
Roche Research Center, Hoffmann-La Roche Inc., 340 Kingsland Street, Nutley, NJ 07110, USA. xin-jie.chu@roche.com
Bartkovitz
David
D
Danho
Waleed
W
Swistok
Joseph
J
Cheung
Adrian Wai-Hing
AW
Kurylko
Grazyna
G
Rowan
Karen
K
Yeon
Mitch
M
Franco
Lucia
L
Qi
Lida
L
Chen
Li
L
Yagaloff
Keith
K
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
C506369:1-amino-4-phenylcyclohexane-1-carboxylic acid; D002264:Carboxylic Acids; D003510:Cyclohexanes; D044102:Receptor, Melanocortin, Type 1; D044105:Receptor, Melanocortin, Type 4