Biological Activities of Melanotropic Peptide Fatty Acid Conjugates

MAC E. HADLEY, FAHAD AL‐OBEIDI, VICTOR J. HRUBY, JONATHAN C. WEINRACH, DOUGLAS FREEDBERG, JINWEN JIANG, RACHEL S. STOVER

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Four fatty acids (FA, palmitic, myristic, decanoic, hexanoic) were individually conjugated to the N‐terminus of the α‐MSH fragment analog, H‐Asp5‐His6‐D‐Phe7‐Arg8‐Trp9‐Lys10‐NH2. This resulted in enhanced potency of the conjugates (compared to the unconjugated melanotropin analog) as determined in the lizard skin bioassay and in the mouse melanoma cell tyrosinase bioassay. The shorter conjugates of hexanoic and decanoic acid were at least equipotent to α‐MSH in the lizard skin bioassay, whereas the longer myristoyl and palmitoyl analogs were 100 times less active. The myristoyl and palmitoyl conjugates exhibited a “creeping” potency in the lizard skin bioassay—that is, potency of the peptides increased with time in contact with the skins. These observations may be related to the more lipid nature of these FA‐conjugates. In the tyrosinase assay, the conjugates were 10–100 times more active than α‐MSH or the unconjugated analog. Each of the FA‐melanotropic peptide conjugates exhibited prolonged (residual) melanotropic activity in both the lizard skin and melanoma cell bioassays. In other words, after removal of the melanotropin conjugates from contact with the skins or cells, responses were still manifested for hours or days thereafter. As little as 1 hr of contact with melanoma cells resulted in enhanced enzyme activity as measured 48 hr later. Since the conjugates, but not H‐[Ast5,D‐Phe7,Lys10]α‐MSH510‐NH2, exhibited prolonged activity, the conversion of reversible agonists to irreversible agonists was demonstrated.

Original languageEnglish (US)
Pages (from-to)180-185
Number of pages6
JournalPigment Cell Research
Volume4
Issue number4
DOIs
StatePublished - Oct 1991

Keywords

  • MSH
  • Melanocyte stimulating hormone
  • Melanocytes
  • Melanogenesis
  • Melanoma
  • Melanotropin

ASJC Scopus subject areas

  • Agronomy and Crop Science
  • Plant Science
  • Developmental Biology
  • Clinical Biochemistry
  • Cell Biology

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