Abstract
α-Melanocyte-stimulating hormone (α-melanotropin; α-MSH) is a linear tridecapeptide (Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2) that reversibily darkens amphibian skins by stimulating melanosome (pigment granule) dispersion within melanophores. By using a number of in vitro melanocyte assays, we have examined the conformational requirements for α-MSH activity. Synthesis of [half-Cys4,half-Cys10]-α-MSH, a cyclic, conformationally restricted, 'isosteric' analogue of α-MSH, provided a melanotropin with a potency > 10,000 times that of the native hormone in stimulating frog (Rana pipiens) skin darkening. The cyclic analogue also showed substantially prolonged activity relative to the native hormone. [half-Cys4,half-Cys10]-α-MSH was ≃30 times more potent than α-MSH in stimulating lizard (Anolis carolinensis) skin melanophores in vitro. By using a cell-free Cloudman S-91 mouse melanoma plasma membrane preparation, we found the cyclic analogue to be ≃3 times as potent as the native hormone in stimulating adenylate cyclase activity. These results provide insight into the conformational requirements for biological activity of α-MSH, and the comparative conformational requirements of α-MSH at a number of pigment cell receptors.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1751-1755 |
| Number of pages | 5 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 79 |
| Issue number | 6 I |
| State | Published - 1982 |
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ASJC Scopus subject areas
- General
- Genetics
Cite this
[half-Cys4,half-Cys10]-α-Melanocyte-stimulating hormone : A cyclic α-melanotropin exhibiting superagonist biological activity. / Sawyer, T. K.; Hruby, Victor J; Darman, P. S.; Hadley, M. E.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 79, No. 6 I, 1982, p. 1751-1755.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - [half-Cys4,half-Cys10]-α-Melanocyte-stimulating hormone
T2 - A cyclic α-melanotropin exhibiting superagonist biological activity
AU - Sawyer, T. K.
AU - Hruby, Victor J
AU - Darman, P. S.
AU - Hadley, M. E.
PY - 1982
Y1 - 1982
N2 - α-Melanocyte-stimulating hormone (α-melanotropin; α-MSH) is a linear tridecapeptide (Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2) that reversibily darkens amphibian skins by stimulating melanosome (pigment granule) dispersion within melanophores. By using a number of in vitro melanocyte assays, we have examined the conformational requirements for α-MSH activity. Synthesis of [half-Cys4,half-Cys10]-α-MSH, a cyclic, conformationally restricted, 'isosteric' analogue of α-MSH, provided a melanotropin with a potency > 10,000 times that of the native hormone in stimulating frog (Rana pipiens) skin darkening. The cyclic analogue also showed substantially prolonged activity relative to the native hormone. [half-Cys4,half-Cys10]-α-MSH was ≃30 times more potent than α-MSH in stimulating lizard (Anolis carolinensis) skin melanophores in vitro. By using a cell-free Cloudman S-91 mouse melanoma plasma membrane preparation, we found the cyclic analogue to be ≃3 times as potent as the native hormone in stimulating adenylate cyclase activity. These results provide insight into the conformational requirements for biological activity of α-MSH, and the comparative conformational requirements of α-MSH at a number of pigment cell receptors.
AB - α-Melanocyte-stimulating hormone (α-melanotropin; α-MSH) is a linear tridecapeptide (Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2) that reversibily darkens amphibian skins by stimulating melanosome (pigment granule) dispersion within melanophores. By using a number of in vitro melanocyte assays, we have examined the conformational requirements for α-MSH activity. Synthesis of [half-Cys4,half-Cys10]-α-MSH, a cyclic, conformationally restricted, 'isosteric' analogue of α-MSH, provided a melanotropin with a potency > 10,000 times that of the native hormone in stimulating frog (Rana pipiens) skin darkening. The cyclic analogue also showed substantially prolonged activity relative to the native hormone. [half-Cys4,half-Cys10]-α-MSH was ≃30 times more potent than α-MSH in stimulating lizard (Anolis carolinensis) skin melanophores in vitro. By using a cell-free Cloudman S-91 mouse melanoma plasma membrane preparation, we found the cyclic analogue to be ≃3 times as potent as the native hormone in stimulating adenylate cyclase activity. These results provide insight into the conformational requirements for biological activity of α-MSH, and the comparative conformational requirements of α-MSH at a number of pigment cell receptors.
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M3 - Article
VL - 79
SP - 1751
EP - 1755
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 6 I
ER -