Related Experiment Video
Updated: Feb 19, 2026
Pharmacologic Induction of Epidermal Melanin and Protection Against Sunburn in a Humanized Mouse Model
Published on: September 7, 2013
Design of MC1R Selective γ-MSH Analogues with Canonical Amino Acids Leads to Potency and Pigmentation
Yang Zhou1, Saghar Mowlazadeh Haghighi1, Ioanna Zoi1
1Department of Chemistry and Biochemistry, The University of Arizona , Tucson, Arizona 85721, United States.
Abstract:
Melanoma is a lethal form of skin cancer. Skin pigmentation, which is regulated by the melanocortin 1 receptor (MC1R), is an effective protection against melanoma. However, the endogenous MC1R agonists lack selectivity for the MC1R and thus can have side effects. The use of noncanonical amino acids in previous MC1R ligand development raises safety concerns. Here we report the development of the first potent and selective hMC1R agonist with only canonical amino acids. Using γ-MSH as a template, we developed a peptide, [Leu3, Leu7, Phe8]-γ-MSH-NH2 (compound 5), which is 16-fold selective for the hMC1R (EC50 = 4.5 nM) versus other melanocortin receptors. Conformational studies revealed a constrained conformation for this linear peptide. Molecular docking demonstrated a hydrophobic binding pocket for the melanocortin 1 receptor. In vivo pigmentation study shows high potency and short duration. [Leu3, Leu7, Phe8]-γ-MSH-NH2 is ideal for inducing short-term skin pigmentation without sun for melanoma prevention.
Insights
Researchers developed a new peptide agonist for the human melanocortin 1 receptor (hMC1R) using only standard amino acids. This potent and selective compound offers a safer way to induce skin pigmentation for melanoma prevention.
Area of Science:
- Biochemistry
- Dermatology
- Medicinal Chemistry
Background:
- Melanoma is a dangerous skin cancer.
- Skin pigmentation, regulated by the melanocortin 1 receptor (MC1R), protects against melanoma.
- Existing MC1R agonists lack selectivity and can cause side effects; noncanonical amino acids raise safety concerns.
Purpose of the Study:
- To develop the first potent and selective human MC1R (hMC1R) agonist using only canonical amino acids.
- To create a safer alternative for melanoma prevention through induced skin pigmentation.
Main Methods:
- Designed a peptide, [Leu3, Leu7, Phe8]-γ-MSH-NH2 (compound 5), based on γ-MSH.
- Conducted conformational studies and molecular docking to analyze peptide structure and binding.
- Performed in vivo studies to assess pigmentation effects.
Main Results:
- Compound 5 exhibits 16-fold selectivity for hMC1R over other melanocortin receptors (EC50 = 4.5 nM).
- Conformational analysis revealed a constrained structure for the linear peptide.
- Molecular docking identified a hydrophobic binding pocket specific to MC1R.
- In vivo studies demonstrated high potency and short duration of induced skin pigmentation.
Conclusions:
- [Leu3, Leu7, Phe8]-γ-MSH-NH2 is a potent and selective hMC1R agonist composed solely of canonical amino acids.
- This peptide is suitable for short-term, sunless skin pigmentation, offering a promising strategy for melanoma prevention.
More Related Videos
09:53Using X-ray Crystallography, Biophysics, and Functional Assays to Determine the Mechanisms Governing T-cell Receptor Recognition of Cancer Antigens
Published on: February 6, 2017
10:05Stimulation of Stem Cell Niches and Tissue Regeneration in Mouse Skin by Switchable Protoporphyrin IX-Dependent Photogeneration of Reactive Oxygen Species In Situ
Published on: May 8, 2020