Biological activities of melanotropic peptide fatty acid conjugates.

M. E. Hadley, F. al-Obeidi, Victor J Hruby, J. C. Weinrach, D. Freedberg, J. W. Jiang, R. S. Stover

Research output: Contribution to journalArticle

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Abstract

Four fatty acids (FA, palmitic, myristic, decanoic, hexanoic) were individually conjugated to the N-terminus of the alpha-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 alpha-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 alpha-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-[Asp5, D-Phe7, Lys10]alpha-MSH5-10-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
StatePublished - Oct 1991

Fingerprint

Bioactivity
skin (animal)
Bioassay
bioactive properties
Skin
Biological Assay
Lizards
Fatty Acids
peptides
fatty acids
alpha-melanocyte-stimulating hormone
bioassays
alpha-MSH
Peptides
lizards
melanoma
melanocyte-stimulating hormone
Melanocyte-Stimulating Hormones
Melanoma
Monophenol Monooxygenase

ASJC Scopus subject areas

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

Cite this

Hadley, M. E., al-Obeidi, F., Hruby, V. J., Weinrach, J. C., Freedberg, D., Jiang, J. W., & Stover, R. S. (1991). Biological activities of melanotropic peptide fatty acid conjugates. Pigment Cell Research, 4(4), 180-185.

Biological activities of melanotropic peptide fatty acid conjugates. / Hadley, M. E.; al-Obeidi, F.; Hruby, Victor J; Weinrach, J. C.; Freedberg, D.; Jiang, J. W.; Stover, R. S.

In: Pigment Cell Research, Vol. 4, No. 4, 10.1991, p. 180-185.

Research output: Contribution to journalArticle

Hadley, ME, al-Obeidi, F, Hruby, VJ, Weinrach, JC, Freedberg, D, Jiang, JW & Stover, RS 1991, 'Biological activities of melanotropic peptide fatty acid conjugates.', Pigment Cell Research, vol. 4, no. 4, pp. 180-185.
Hadley ME, al-Obeidi F, Hruby VJ, Weinrach JC, Freedberg D, Jiang JW et al. Biological activities of melanotropic peptide fatty acid conjugates. Pigment Cell Research. 1991 Oct;4(4):180-185.
Hadley, M. E. ; al-Obeidi, F. ; Hruby, Victor J ; Weinrach, J. C. ; Freedberg, D. ; Jiang, J. W. ; Stover, R. S. / Biological activities of melanotropic peptide fatty acid conjugates. In: Pigment Cell Research. 1991 ; Vol. 4, No. 4. pp. 180-185.
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abstract = "Four fatty acids (FA, palmitic, myristic, decanoic, hexanoic) were individually conjugated to the N-terminus of the alpha-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 alpha-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 alpha-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-[Asp5, D-Phe7, Lys10]alpha-MSH5-10-NH2, exhibited prolonged activity, the conversion of reversible agonists to irreversible agonists was demonstrated.",
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AU - Hruby, Victor J

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AU - Freedberg, D.

AU - Jiang, J. W.

AU - Stover, R. S.

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