Receptor binding affinities and biological activities of linear and cyclic melanocortins in B16 murine melanoma cells expressing the native MC1 receptor: J Pharm Pharmacol

U. G. Sahm, G. W. Olivier, S. K. Branch, S. H. Moss, C. W. Pouton

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Cyclic alpha-melanocyte-stimulating hormone (alpha-MSH) analogues produced by disulphide bridging (e.g. [Cys4,Cys10] alpha-MSH) are known to be almost equipotent to the native hormone in amphibian skin bioassays and as a consequence have been proposed as a paradigm for the active conformation of native MSH at the pigment cell MC1 receptor. However this proposal has been somewhat speculative as there is no published data comparing biological activity of cyclic MSH analogues with data on receptor binding. This study addresses this problem by comparing tyrosinase stimulatory activity with their receptor binding affinity in B16 murine melanoma cells expressing the native MC1 melanocortin receptor. Cyclic [Cys4,Cys10] alpha-MSH showed almost the same affinity for the MC1 receptor as alpha-MSH, but the linear analogue [Cys4,Cys10] alpha-MSH bound less strongly. Both had biological activities similar to that of the natural ligand. Introduction of D-Phe into the ring in position 7 increased both affinity and activity of the cyclic compound. The study suggests that the intrinsic efficacy of cyclic [Cys4,Cys10] alpha-MSH analogues is similar to native alpha-MSH. Our studies support the proposal that the cyclic structure serves as a good model for the active conformation of linear alpha-MSH.
Original languageEnglish
Pages (from-to)197-200
Number of pages4
JournalJournal of Pharmacy and Pharmacology
Volume48
Publication statusPublished - 1996

Keywords

  • Binding, Competitive Melanoma, Experimental/metabolism Molecular Structure Receptors, Corticotropin/*metabolism Receptors, Melanocortin alpha-MSH/analogs & derivatives/chemistry/*metabolism

Cite this

@article{b1c3a8605d1d4efbb14264e5764904d0,
title = "Receptor binding affinities and biological activities of linear and cyclic melanocortins in B16 murine melanoma cells expressing the native MC1 receptor: J Pharm Pharmacol",
abstract = "Cyclic alpha-melanocyte-stimulating hormone (alpha-MSH) analogues produced by disulphide bridging (e.g. [Cys4,Cys10] alpha-MSH) are known to be almost equipotent to the native hormone in amphibian skin bioassays and as a consequence have been proposed as a paradigm for the active conformation of native MSH at the pigment cell MC1 receptor. However this proposal has been somewhat speculative as there is no published data comparing biological activity of cyclic MSH analogues with data on receptor binding. This study addresses this problem by comparing tyrosinase stimulatory activity with their receptor binding affinity in B16 murine melanoma cells expressing the native MC1 melanocortin receptor. Cyclic [Cys4,Cys10] alpha-MSH showed almost the same affinity for the MC1 receptor as alpha-MSH, but the linear analogue [Cys4,Cys10] alpha-MSH bound less strongly. Both had biological activities similar to that of the natural ligand. Introduction of D-Phe into the ring in position 7 increased both affinity and activity of the cyclic compound. The study suggests that the intrinsic efficacy of cyclic [Cys4,Cys10] alpha-MSH analogues is similar to native alpha-MSH. Our studies support the proposal that the cyclic structure serves as a good model for the active conformation of linear alpha-MSH.",
keywords = "Binding, Competitive Melanoma, Experimental/metabolism Molecular Structure Receptors, Corticotropin/*metabolism Receptors, Melanocortin alpha-MSH/analogs & derivatives/chemistry/*metabolism",
author = "Sahm, {U. G.} and Olivier, {G. W.} and Branch, {S. K.} and Moss, {S. H.} and Pouton, {C. W.}",
note = "M1 - 2 Sahm, U G Olivier, G W Branch, S K Moss, S H Pouton, C W eng Research Support, Non-U.S. Gov't ENGLAND 1996/02/01 J Pharm Pharmacol. 1996 Feb;48(2):197-200.",
year = "1996",
language = "English",
volume = "48",
pages = "197--200",
journal = "Journal of Pharmacy and Pharmacology",
issn = "0022-3573",
publisher = "Wiley-Blackwell",

}

Receptor binding affinities and biological activities of linear and cyclic melanocortins in B16 murine melanoma cells expressing the native MC1 receptor : J Pharm Pharmacol. / Sahm, U. G.; Olivier, G. W.; Branch, S. K.; Moss, S. H.; Pouton, C. W.

In: Journal of Pharmacy and Pharmacology, Vol. 48, 1996, p. 197-200.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Receptor binding affinities and biological activities of linear and cyclic melanocortins in B16 murine melanoma cells expressing the native MC1 receptor

T2 - J Pharm Pharmacol

AU - Sahm, U. G.

AU - Olivier, G. W.

AU - Branch, S. K.

AU - Moss, S. H.

AU - Pouton, C. W.

N1 - M1 - 2 Sahm, U G Olivier, G W Branch, S K Moss, S H Pouton, C W eng Research Support, Non-U.S. Gov't ENGLAND 1996/02/01 J Pharm Pharmacol. 1996 Feb;48(2):197-200.

PY - 1996

Y1 - 1996

N2 - Cyclic alpha-melanocyte-stimulating hormone (alpha-MSH) analogues produced by disulphide bridging (e.g. [Cys4,Cys10] alpha-MSH) are known to be almost equipotent to the native hormone in amphibian skin bioassays and as a consequence have been proposed as a paradigm for the active conformation of native MSH at the pigment cell MC1 receptor. However this proposal has been somewhat speculative as there is no published data comparing biological activity of cyclic MSH analogues with data on receptor binding. This study addresses this problem by comparing tyrosinase stimulatory activity with their receptor binding affinity in B16 murine melanoma cells expressing the native MC1 melanocortin receptor. Cyclic [Cys4,Cys10] alpha-MSH showed almost the same affinity for the MC1 receptor as alpha-MSH, but the linear analogue [Cys4,Cys10] alpha-MSH bound less strongly. Both had biological activities similar to that of the natural ligand. Introduction of D-Phe into the ring in position 7 increased both affinity and activity of the cyclic compound. The study suggests that the intrinsic efficacy of cyclic [Cys4,Cys10] alpha-MSH analogues is similar to native alpha-MSH. Our studies support the proposal that the cyclic structure serves as a good model for the active conformation of linear alpha-MSH.

AB - Cyclic alpha-melanocyte-stimulating hormone (alpha-MSH) analogues produced by disulphide bridging (e.g. [Cys4,Cys10] alpha-MSH) are known to be almost equipotent to the native hormone in amphibian skin bioassays and as a consequence have been proposed as a paradigm for the active conformation of native MSH at the pigment cell MC1 receptor. However this proposal has been somewhat speculative as there is no published data comparing biological activity of cyclic MSH analogues with data on receptor binding. This study addresses this problem by comparing tyrosinase stimulatory activity with their receptor binding affinity in B16 murine melanoma cells expressing the native MC1 melanocortin receptor. Cyclic [Cys4,Cys10] alpha-MSH showed almost the same affinity for the MC1 receptor as alpha-MSH, but the linear analogue [Cys4,Cys10] alpha-MSH bound less strongly. Both had biological activities similar to that of the natural ligand. Introduction of D-Phe into the ring in position 7 increased both affinity and activity of the cyclic compound. The study suggests that the intrinsic efficacy of cyclic [Cys4,Cys10] alpha-MSH analogues is similar to native alpha-MSH. Our studies support the proposal that the cyclic structure serves as a good model for the active conformation of linear alpha-MSH.

KW - Binding, Competitive Melanoma, Experimental/metabolism Molecular Structure Receptors, Corticotropin/metabolism Receptors, Melanocortin alpha-MSH/analogs & derivatives/chemistry/metabolism

M3 - Article

VL - 48

SP - 197

EP - 200

JO - Journal of Pharmacy and Pharmacology

JF - Journal of Pharmacy and Pharmacology

SN - 0022-3573

ER -