摘要
背景:肽在皮肤中起决定性的作用,从宿主防御反应到各种形式的细胞和细胞器官功能的神经内分泌调节。与放射性核素或光敏剂缀合的合成肽可用于鉴定和治疗皮肤肿瘤及其在身体其他器官中的转移形式。在本次评论的介绍性部分,简要总结了不同肽在皮肤中的作用和相互作用,包括其对经常发生的皮肤癌的潜在应用。特别强调治疗黑色素瘤和黑色素瘤病变的不同靶向选择。 放射性核素靶向:α-黑素细胞激素(α-MSH)是通过由黑素瘤细胞和黑素细胞表达的G蛋白偶联的黑皮质素-1受体的靶向黑素瘤肿瘤的最突出的肽。用111In,67 / 68Ga,64Cu,90Y,212Pb,99mTc,188Re的含有α-MSH的螯合剂的100多种不同的线性和环状类似物被合成并用实验动物和一些临床研究检验。线性Ac-Nle-Asp-His-D-Phe-Arg-Trp-Gly-Lys-NH 2(NAP-酰胺)和再环化的Cys-Cys-Glu-His-D-Phe-Arg-Trp-Cys-Arg 在N或C末端含有不同螯合剂的-Pro-Val-NH2(Re [Arg11] CCMSH)作为具有进一步优化特性的肽药物的铅化合物。或者,黑素瘤可以与结合在这些肿瘤中细胞外发生的黑色素颗粒结合的放射性肽靶向。 光敏剂定位:最近的一种方法是使用特异性激活光敏剂的LED或相干激光将附着于MSH分子的光敏剂应用于靶向光动力疗法。实验研究表明,与放射性核素相比,该方法可行性更为温和方便。
关键词: 黑素细胞激素(MSH),黑皮质素-1受体(MC1R),放射性金属,光敏剂,恶性黑素瘤,转移,黑色素结合肽,光动力疗法。
Current Medicinal Chemistry
Title:Synthetic Peptide Drugs for Targeting Skin Cancer: Malignant Melanoma and Melanotic Lesions
Volume: 24 Issue: 17
关键词: 黑素细胞激素(MSH),黑皮质素-1受体(MC1R),放射性金属,光敏剂,恶性黑素瘤,转移,黑色素结合肽,光动力疗法。
摘要: 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
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Cite this article as:
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 |
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