DIVERGENT MELANOPHORE-DISPERSING AND TYROSINASE-STIMULATING ACTIVITY OF SYNTHETIC LEUCINE9-ALPHA-MELANOTROPIN

Leucine9-.alpha.-melanotropin ([Leu9].alpha.-MSH) was synthesized in homogeneous solution by a fragment condensation approach, and it was assayed for its melanophore-dispersing and its tyrosinase-stimulating activity with a reflectometric in vitro frog skin assay and with cultured mouse melanoma cells, respectively. In both assay systems, parallel log dose-response curves were obtained for [Leu9].alpha.-MSH and .alpha.-MSH; in the frog skin assay the activity of the title compound was 1 .cntdot. 1010 U/mmol, i.e., 25% of the activity of .alpha.-MSH, whereas its tyrosinase-stimulating potency was only 1% compared to .alpha.-MSH (EC50 [median effective concentration] = 2.5 .cntdot. 10-7 M). This indicates a major difference in the recognition/stimulation process of the receptors of the 2 cell types.