Synthetic Peptide Drugs for Targeting Skin Cancer: Malignant Melanoma and Melanotic Lesions

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.

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