Synthesis and Biological Evaluation of the Superagonist [Nα-Chlorotriazinylaminofluorescein-Ser1, Nle4, D-Phe7]-α-MSH

Abstract

The fluorescein-labeled melanotropin [N″-chlorotriazinyl-aminofluorescein-Ser1, Nle4, D-Phe7]-α-MSH, was prepared by solid-phase techniques of peptide synthesis. The biological actions of this analogue were determined in several melanocyte bioassays and were compared with the parent peptide [Nle4, D-Phe7]-α-MSH and the native hormone α-MSH. The fluorescein compound was a superpotent agonist with ~10 times more activity than α-MSH in both the frog and the lizard skin bioassays. Murine S91 melanoma cells assayed in vitro (tyrosinase bioassay) were as responsive to the fluorescein analogue as to α-MSH. The analogue exhibited ultraprolonged biological activity and the biological activities were unaffected by treatment of the analogue with α-chymotrypsin. The fluorescein-labeled melanotropin should prove useful for melanotropin receptor characterization.