Linear and cyclic alpha-melanotropin [4-10]-fragment analogues that exhibit superpotency and residual activity.

M. E. Hadley, M. M. Marwan, F. al-Obeidi, Victor J Hruby, A. M. Castrucci

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Abstract

Two analogues of alpha-MSH (Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2), Ac-[Nle4, Asp5, D-Phe7, Lys10]alpha-MSH4-10NH2 and Ac-[Nle4, Asp5, D-Phe7, Lys10] alpha-MSH4-10-NH2, were synthesized, and the melanotropic activities of the peptides were compared in several bioassays. Potencies were determined in the in vitro frog and lizard skin bioassays and in the S91 melanoma cell tyrosinase assay. Both analogues were equipotent or more potent than alpha-MSH in all bioassays, and the activities of the analogues were prolonged compared to alpha-MSH. The two analogues were very resistant to inactivation by purified proteolytic enzymes (alpha-chymotrypsin, trypsin, and pepsin). The two peptides could be topically applied and transdermally delivered across the skin of mice in vivo, resulting in a shift from pheomelanogenesis to eumelanogenesis within follicular melanocytes. The cyclic analogue exhibited greater potency, prolonged activity, and stability against enzyme inactivation than did the linear peptide. The significance of the findings for the further design of melanotropin analogues is discussed, as in the possible relevance of these melanotropin analogues for use in biomedical studies.

Original languageEnglish (US)
Pages (from-to)478-484
Number of pages7
JournalPigment Cell Research
Volume2
Issue number6
StatePublished - Nov 1989

Fingerprint

alpha-melanocyte-stimulating hormone
alpha-MSH
Bioassay
melanocyte-stimulating hormone
Biological Assay
Melanocyte-Stimulating Hormones
bioassays
peptides
skin (animal)
Peptides
Skin
Enzyme Stability
enzyme inactivation
Lizards
melanocytes
Monophenol Monooxygenase
Pepsin A
Melanocytes
chymotrypsin
pepsin

ASJC Scopus subject areas

  • Agronomy and Crop Science

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Linear and cyclic alpha-melanotropin [4-10]-fragment analogues that exhibit superpotency and residual activity. / Hadley, M. E.; Marwan, M. M.; al-Obeidi, F.; Hruby, Victor J; Castrucci, A. M.

In: Pigment Cell Research, Vol. 2, No. 6, 11.1989, p. 478-484.

Research output: Contribution to journalArticle

Hadley, M. E. ; Marwan, M. M. ; al-Obeidi, F. ; Hruby, Victor J ; Castrucci, A. M. / Linear and cyclic alpha-melanotropin [4-10]-fragment analogues that exhibit superpotency and residual activity. In: Pigment Cell Research. 1989 ; Vol. 2, No. 6. pp. 478-484.
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