Synthesis and biological evaluation of the superagonist [N^α‐chlorotriazinylaminofluorescein‐Ser¹, Nle⁴, D‐Phe⁷]‐α‐MSH

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.