Melanotropin structure-activity studies on melanocytes of the teleost fish, Synbranchus marmoratus

The minimal sequence of α-MSH required for full agonism on fish (Synbranchus marmoratus) melanocytes was determined to be Ac-α-MSH_5-10-NH₂ since Ac-α-MSH_6-10-NH₂ and Ac-α-MSH_6-9-NH₂ were inactive. The N-terminal tripeptide sequence, Ser-Tyr-Ser, lacked any contribution to potency since the 4-13 (Ac-[Nle⁴]-α-MSH_4-13-NH₂) sequence was equipotent to α-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-α-MSH_4-10-NH₂ was about 100 times more potent than the Ac-α-MSH_5-10-NH₂ sequence, and Ac-[Nle₄]-α-MSH_4-13-NH₂ was about 10 times more active than Ac-[Nle⁴]-α-MSH_4-12-NH₂. The minimal sequence for equipotency to α-MSH was demonstrated to be Ac-[Nle⁴]-α-MSH_4-13-NH₂. [Nle⁴, d-Phe⁷]-α-MSH was about 10 times more active than α-MSH. Unexpectingly, several conformationally restricted cyclic melanotropins were either partial agonists ([Cys⁴, Cys¹⁰]-α-MSH) or totally inactive (Ac[Cys⁴, Cys¹⁰]-α-MSH_4-10-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.