Synthesis and Biological Activities of Fatty Acid Conjugates of a Cyclic Lactamα-Melanotropin

Fahad Al-Obeidi, Victor J. Hruby, Nader Yaghoubi, Mohamed M. Marwan, E. Mac Hadley

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25 Scopus citations


Four fatty acid conjugates of a cyclic lactam-bridged α-MSH fragment analogue were synthesized and their potencies and biological activities compared in several melanotropin bioassays. Palmitoyl, myristoyl, decanoyl, and hexanoyl conjugates of H-Asp-His-D-Phe-Arg-Trp-Lys-NH2 were prepared. In the in vitro mouse melanoma cell assay, each of the conjugates was 10-100 times more potent than α-MSH or the substrate peptide in elevating tyrosinase activity. The shorter conjugates of hexanoic and decanoic acid were as potent as α-MSH in the lizard skin bioassay, whereas the longer myristoyl and palmitoyl analogues were about 100 times less potent. The potency of the myristoyl and palmitoyl conjugates increased with time in contact with the skins. These observations may be related to the more lipid-like nature of these peptide-fatty acid conjugates. Each of the conjugates exhibited prolonged melanotropic activity in the lizard skin bioassays and in the mouse S91 melanoma tyrosinase bioassay, since the biological response continued following removal of the conjugates from the incubation media. The prolonged residual melanotropic activity resulted from conjugation of the fatty acids to the MSH fragment analogue since the analogue itself did not exhibit prolonged activity.

Original languageEnglish (US)
Pages (from-to)118-123
Number of pages6
JournalJournal of Medicinal Chemistry
Issue number1
StatePublished - Jan 1 1992

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery


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