Semi-rigid tripeptide agonists of melanocortin receptors.
A series of 30 RCO-HfR-NH(2) derivatives show preference for the mouse MC1R vs MC3-5Rs. trans-4-HOC(6)H(4)CH=CHCO-HfR-NH(2) (13) [EC(50) (nM): MC1R 83, MC3R 20500, MC4R 18130 and MC5R 935; ratio 1:246:217:11] is 11 times more potent than the lead compound LK-394 Ph(CH(2))(3)CO-HfR-NH(2) (2) and only 11 times less potent than the native tridecapeptide alpha-MSH at mMC1R. Differences in conformations of 2 and 13 are discussed.
Ruwe
Andrew R
AR
University of Cincinnati, James L. Winkle College of Pharmacy, Cincinnati, OH 45267, USA.
Koikov
Leonid
L
Abdel-Malek
Zalfa
Z
Haskell-Luevano
Carrie
C
Dirain
Marvin L
ML
Portillo
Federico
F
Xiang
Zhimin
Z
Wortman
Matt
M
Knittel
James J
JJ
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D003198:Computer Simulation; D051379:Mice; D008968:Molecular Conformation; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D020033:Protein Isoforms / Q000819:agonists / Q000378:metabolism; D044101:Receptors, Melanocortin / Q000819:agonists* / Q000378:metabolism; D000521:alpha-MSH / Q000737:chemistry
D010455:Peptides; D020033:Protein Isoforms; D044101:Receptors, Melanocortin; D000521:alpha-MSH