Melanotropin Receptors I. Synthesis and Biological Activity of Nα‐(5‐Bromovaleryl)‐Nα‐deacetyl‐α‐melanotropin

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Abstract
Chemical synthesis and biological activities of a new α‐melanotropin derivative are described. Nα‐(5‐Bromovaleryl)‐Nα‐deacetyl‐α‐melanotropin contains the 5‐bromopentanoyl group as a chemical ‘handle’ in place of the acetyl group of the natural hormone. The synthesis involved a new protected intermediate which allowed the selective deprotection of either the Nα or Nα amino group. The title compound reacted with sodium thiosulfate to give Nα‐deacetyl‐Nα‐(5‐(sulfothio)valeryl)‐α‐melanotropin, a key intermediate for the preparation of tobaccomosaic virus/α‐melanotropin disulfide conjugates. As a basis for the study of the conjugates, biological activities of the title compound on Cloudman S‐91 mouse melanoma cell cultures (tyrosinase stimulation, binding, and cyclic AMP accumulation) were determined. They proved to be quite similar to the corresponding α‐melanotropin activities. Differences in bindings may be explained by stronger hydrophobic interaction of the new derivative with the lipid phase of the target cell membranes.