Investigation of the role of tryptophan in alpha-MSH. Replacement by L-pentamethylphenylalanine and L-phenylalanine.

Two analogues of alpha-MSH are described, in which the tryptophan residue occuring in position 9 of the natural hormone has been replaced by pentamethylphenylalanine and phenylalanine, respectively. The analogues were synthesized via a conventional procedure and the [Phe9]-analogue also by a semi-synthetic approach, which demonstrated the favourable properties of the applied, new amino-protecting Msc function for this purpose. The widely different electron donor properties of the substituted residues were accompanied by a large difference in melanocyte stimulating activity of the analogues. The [Pmp9]-analogue, having donor properties comparable to those of the natural compound, was four to five times more active than the analogue containing the poorly donating Phe residue. The opposite effect was noted in in vivo lipolysis in rabbits.