Abstract
Melanoma incidence continues to rise due to intentional exposure to ultraviolet radiation (UVR) from sunlight and indoor tanning beds. Eumelanin exhibits photoprotective effects; thus, agents that induce its synthesis offer a means for sunless tanning without UVR damage. Herein, we report the development of two pentapeptides, P9 and P10, capable of enhancing melanin synthesis in B16 melanoma cells by activating mushroom and mouse tyrosinases without any effect on cell viability or proliferation. P9 and P10 significantly increased melanin content in a dose-dependent manner comparable to the positive controls, IBMX, scoparone, and α-MSH. However, unlike IBMX and scoparone, but similar to α-MSH, P9 and P10 were able to reverse 6BH4-dependent tyrosinase inhibition. We hypothesize that P9 and P10 allosterically activate tyrosinase and consequently enhance epidermal melanin synthesis. P9 and P10 may offer an alternative to tanning bed use and non-photoprotective tanning products. Moreover, sustained increase of melanin content in skin has the potential to reduce symptoms of photosensitivity disorders such as erythropoietic protoporphyria (EPP), solar urticaria (SU) and polymorphic light eruption (PLE), which lack fully effective treatments and result in significant morbidity.
Keywords: Allosteric activation, melanin content, melanoma, pentapeptide, tanning beds, tyrosinase.
Current Topics in Medicinal Chemistry
Title:Novel Pentapeptide Activators of Mammalian and Mushroom Tyrosinase
Volume: 14 Issue: 12
Author(s): Anan Abu Ubeid and Basil M. Hantash
Affiliation:
Keywords: Allosteric activation, melanin content, melanoma, pentapeptide, tanning beds, tyrosinase.
Abstract: Melanoma incidence continues to rise due to intentional exposure to ultraviolet radiation (UVR) from sunlight and indoor tanning beds. Eumelanin exhibits photoprotective effects; thus, agents that induce its synthesis offer a means for sunless tanning without UVR damage. Herein, we report the development of two pentapeptides, P9 and P10, capable of enhancing melanin synthesis in B16 melanoma cells by activating mushroom and mouse tyrosinases without any effect on cell viability or proliferation. P9 and P10 significantly increased melanin content in a dose-dependent manner comparable to the positive controls, IBMX, scoparone, and α-MSH. However, unlike IBMX and scoparone, but similar to α-MSH, P9 and P10 were able to reverse 6BH4-dependent tyrosinase inhibition. We hypothesize that P9 and P10 allosterically activate tyrosinase and consequently enhance epidermal melanin synthesis. P9 and P10 may offer an alternative to tanning bed use and non-photoprotective tanning products. Moreover, sustained increase of melanin content in skin has the potential to reduce symptoms of photosensitivity disorders such as erythropoietic protoporphyria (EPP), solar urticaria (SU) and polymorphic light eruption (PLE), which lack fully effective treatments and result in significant morbidity.
Export Options
About this article
Cite this article as:
Ubeid Abu Anan and Hantash M. Basil, Novel Pentapeptide Activators of Mammalian and Mushroom Tyrosinase, Current Topics in Medicinal Chemistry 2014; 14 (12) . https://dx.doi.org/10.2174/1568026614666140523115732
DOI https://dx.doi.org/10.2174/1568026614666140523115732 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
KSP Inhibitors as Antimitotic Agents
Current Topics in Medicinal Chemistry Anti-Cancer Therapeutic Approaches Based on Intracellular and Extracellular Heat Shock Proteins
Current Medicinal Chemistry Targeting Apoptosis Pathways in Cancer Therapy
Current Cancer Drug Targets Monitoring T Cell Responses to Cancer Immunotherapy: Can We Now Identify Biomarkers Predicting Patients Who will be Responders
Current Cancer Therapy Reviews The ABCA2 Transporter: Intracellular Roles in Trafficking and Metabolism of LDL-Derived Cholesterol and Sterol-Related Compounds
Current Drug Metabolism Unveiling the Role of Nuclear Transport in Epithelial-to-Mesenchymal Transition
Current Cancer Drug Targets Cellular Uptake of Neutral Phosphorodiamidate Morpholino Oligomers
Current Pharmaceutical Biotechnology Pitfalls and Solutions for the Validation of Novel Drugs in Animal Models of Disease
Current Immunology Reviews (Discontinued) Plasticity of T Cell Differentiation and Cytokine Signature: A Double-Edged Sword for Immune Responses
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Gallium in Cancer Treatment
Current Topics in Medicinal Chemistry Effect of Recombinant Human Thymosin-α1, an Immuno-Modulating Peptide with 28 Amino Acids, on the Activity of Cytochrome P450s
Drug Metabolism Letters Dysregulation of Lysyl Oxidases Expression in Diabetic Nephropathy and Renal Cell Carcinoma
Current Drug Targets Aberrant Regulation of Translation Initiation in Tumorigenesis
Current Molecular Medicine Diagnosis and Management of Lynch Syndrome
Recent Patents on Regenerative Medicine Editorial (Thematic Issue: Ceramics, Nanotubes, Advanced Materials: Theoretical and Experimental Structure-Property Relationships Part IV)
Current Physical Chemistry Survivin Modulators: An Updated Patent Review (2011 - 2015)
Recent Patents on Anti-Cancer Drug Discovery III. Angiogenesis: Complexity of Tumor Vasculature and Microenvironment
Current Pharmaceutical Design Hypopituitarism in the Elderly: Multifaceted Clinical and Biochemical Presentation
Current Aging Science Advances in Photodynamic Therapy Assisted by Electroporation
Current Drug Metabolism Recent Advances in Protein and Peptide Drug Delivery: A Special Emphasis on Polymeric Nanoparticles
Protein & Peptide Letters