Melanotropin structure-activity studies on melanocytes of the teleost fish, Synbranchus marmoratus.
The minimal sequence of alpha-MSH required for full agonism on fish (Synbranchus marmoratus) melanocytes was determined to be Ac-alpha-MSH5-10-NH2 since Ac-alpha-MSH6-10-NH2 and Ac-alpha-MSH6-9-NH2 were inactive. The N-terminal tripeptide sequence, Ser-Tyr-Ser, lacked any contribution to potency since the 4-13 (Ac-[Nle4]-alpha-MSH4-13-NH2) sequence was equipotent to alpha-MSH. The important potentiating amino acids were found to be Met at position 4 of the amino terminus and Val at position 13 of the carboxy terminus of the hormone, since Ac-alpha-MSH4-10-NH2 was about 100 times more potent than the Ac-alpha-MSH5-10-NH2 sequence, and Ac-[Nle4]-alpha-MSH4-13-NH2 was about 10 times more active than Ac-[Nle4]-alpha-MSH4-12-NH2. The minimal sequence for equipotency to alpha-MSH was demonstrated to be Ac-[Nle4]-alpha-MSH4-13-NH2. [Nle4, D-Phe7]-alpha-MSH was about 10 times more active than alpha-MSH. Unexpectingly, several conformationally restricted cyclic melanotropins were either partial agonists ([Cys4, Cys10]-alpha-MSH) or totally inactive (Ac[Cys4, Cys10]-alpha-MSH4-10-NH2) on fish melanocytes. These results point out some rather remarkable differences between S. marmoratus and tetrapod melanophores relative to structural requirements for MSH receptor recognition and signal transduction.
Castrucci
A M
AM
Departamento de Fisiologia, Universidade de São Paulo, Brazil.
Hadley
M E
ME
Wilkes
B C
BC
Hruby
V J
VJ
Sawyer
T K
TK
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004524:Eels; D009074:Melanocyte-Stimulating Hormones / Q000031:analogs & derivatives / Q000378:metabolism*; D008544:Melanocytes / Q000378:metabolism*; D009842:Oligopeptides / Q000032:analysis; D013329:Structure-Activity Relationship
D009842:Oligopeptides; D009074:Melanocyte-Stimulating Hormones