Abstract
Background: Peptides play decisive roles in the skin, ranging from host defense responses to various forms of neuroendocrine regulation of cell and organelle function. Synthetic peptides conjugated to radionuclides or photosensitizers may serve to identify and treat skin tumors and their metastatic forms in other organs of the body. In the introductory part of this review, the role and interplay of the different peptides in the skin are briefly summarized, including their potential application for the management of frequently occurring skin cancers. Special emphasis is given to different targeting options for the treatment of melanoma and melanotic lesions.
Radionuclide Targeting: α-Melanocyte-stimulating hormone (α-MSH) is the most prominent peptide for targeting of melanoma tumors via the G protein-coupled melanocortin-1 receptor that is (over-)expressed by melanoma cells and melanocytes. More than 100 different linear and cyclic analogs of α-MSH containing chelators for 111In, 67/68Ga, 64Cu, 90Y, 212Pb, 99mTc, 188Re were synthesized and examined with experimental animals and in a few clinical studies. Linear Ac-Nle-Asp-His-D-Phe-Arg-Trp-Gly-Lys-NH2 (NAP-amide) and Re-cyclized Cys- Cys-Glu-His-D-Phe-Arg-Trp-Cys-Arg-Pro-Val-NH2 (Re[Arg11]CCMSH) containing different chelators at the N- or C-terminus served as lead compounds for peptide drugs with further optimized characteristics. Alternatively, melanoma may be targeted with radiopeptides that bind to melanin granules occurring extracellularly in these tumors. Photosensitizer targeting: A more recent approach is the application of photosensitizers attached to the MSH molecule for targeted photodynamic therapy using LED or coherent laser light that specifically activates the photosensitizer. Experimental studies have demonstrated the feasibility of this approach as a more gentle and convenient alternative compared to radionuclides.Keywords: Melanocyte-stimulating hormone (MSH), melanocortin-1 receptor (MC1R), radiometal, photosensitizer, malignant melanoma, metastasis, melanin-binding peptide, photodynamic therapy.
Current Medicinal Chemistry
Title:Synthetic Peptide Drugs for Targeting Skin Cancer: Malignant Melanoma and Melanotic Lesions
Volume: 24 Issue: 17
Author(s): Alex N. Eberle*, Bhimsen Rout, Mei Bigliardi Qi and Paul L. Bigliardi*
Affiliation:
- Department of Biomedicine, University of Basel,Switzerland
- A*STAR, Biopolis, Singapore; YLL School of Medicine, National University of Singapore NUS and University Medicine Clinic, National University Hospital NUHS,Singapore
Keywords: Melanocyte-stimulating hormone (MSH), melanocortin-1 receptor (MC1R), radiometal, photosensitizer, malignant melanoma, metastasis, melanin-binding peptide, photodynamic therapy.
Abstract: Background: Peptides play decisive roles in the skin, ranging from host defense responses to various forms of neuroendocrine regulation of cell and organelle function. Synthetic peptides conjugated to radionuclides or photosensitizers may serve to identify and treat skin tumors and their metastatic forms in other organs of the body. In the introductory part of this review, the role and interplay of the different peptides in the skin are briefly summarized, including their potential application for the management of frequently occurring skin cancers. Special emphasis is given to different targeting options for the treatment of melanoma and melanotic lesions.
Radionuclide Targeting: α-Melanocyte-stimulating hormone (α-MSH) is the most prominent peptide for targeting of melanoma tumors via the G protein-coupled melanocortin-1 receptor that is (over-)expressed by melanoma cells and melanocytes. More than 100 different linear and cyclic analogs of α-MSH containing chelators for 111In, 67/68Ga, 64Cu, 90Y, 212Pb, 99mTc, 188Re were synthesized and examined with experimental animals and in a few clinical studies. Linear Ac-Nle-Asp-His-D-Phe-Arg-Trp-Gly-Lys-NH2 (NAP-amide) and Re-cyclized Cys- Cys-Glu-His-D-Phe-Arg-Trp-Cys-Arg-Pro-Val-NH2 (Re[Arg11]CCMSH) containing different chelators at the N- or C-terminus served as lead compounds for peptide drugs with further optimized characteristics. Alternatively, melanoma may be targeted with radiopeptides that bind to melanin granules occurring extracellularly in these tumors. Photosensitizer targeting: A more recent approach is the application of photosensitizers attached to the MSH molecule for targeted photodynamic therapy using LED or coherent laser light that specifically activates the photosensitizer. Experimental studies have demonstrated the feasibility of this approach as a more gentle and convenient alternative compared to radionuclides.Export Options
About this article
Cite this article as:
Eberle N. Alex*, Rout Bhimsen, Bigliardi Qi Mei and L. Bigliardi Paul *, Synthetic Peptide Drugs for Targeting Skin Cancer: Malignant Melanoma and Melanotic Lesions, Current Medicinal Chemistry 2017; 24 (17) . https://dx.doi.org/10.2174/0929867324666170605105942
DOI https://dx.doi.org/10.2174/0929867324666170605105942 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread 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
-
Heparin, Heparan Sulfate and Heparanase in Cancer: Remedy for Metastasis?
Anti-Cancer Agents in Medicinal Chemistry The Pivotal Role of Nitric Oxide: Effects on the Nervous and Immune Systems
Current Pharmaceutical Design Antibody Gene Therapy: Getting Closer to Clinical Application?
Current Gene Therapy Doxorubicin-Loaded Nanoparticles: New Advances in Breast Cancer Therapy
Anti-Cancer Agents in Medicinal Chemistry Innovative Cancer Treatments that Augment Radiotherapy or Chemotherapy by the Use of Immunotherapy or Gene Therapy
Recent Patents on Anti-Cancer Drug Discovery Hypertension, Anti-Hypertensive Therapy and Neoplasia
Current Pharmaceutical Design Activation of Macrophages: Establishing a Role for Polysaccharides in Drug Delivery Strategies Envisaging Antibacterial Therapy
Current Pharmaceutical Design Isoliquiritigenin (ISL) and its Formulations: Potential Antitumor Agents
Current Medicinal Chemistry Recent Progress in FKBP Ligand Development
Current Molecular Pharmacology Molecular Mechanisms and Proposed Targets for Selected Anticancer Gold Compounds
Current Topics in Medicinal Chemistry Colon Cancer Therapy: Recent Developments in Nanomedicine to Improve the Efficacy of Conventional Chemotherapeutic Drugs
Anti-Cancer Agents in Medicinal Chemistry Neurokinin-1 Receptor Antagonist Can Prevent the Delayed Phase in Patients: A Single Center Retrospect Study
Anti-Cancer Agents in Medicinal Chemistry Crosstalk between Oxidative and Nitrosative Stress and Arterial Stiffness
Current Vascular Pharmacology NMR-based Drug Development and Improvement Against Malignant Melanoma – Implications for the MIA Protein Family
Current Medicinal Chemistry Natural Compounds in Anti-Leukaemic Therapy: A Review
Mini-Reviews in Medicinal Chemistry Potential Prognostic Predictors and Molecular Targets for Skin Melanoma Screened by Weighted Gene Co-expression Network Analysis
Current Gene Therapy Effect of Electromagnetic Radiations on Neurodegenerative Diseases- Technological Revolution as a Curse in Disguise
CNS & Neurological Disorders - Drug Targets Inhibitors of the Proteolytic Activity of Urokinase Type Plasminogen Activator
Current Pharmaceutical Design Drugs and their Interactions
Current Drug Discovery Technologies Identification of Sets of Cytoskeletal Related and Adhesion-related Coding Region Mutations in the TCGA Melanoma Dataset that Correlate with a Negative Outcome
Current Genomics