Ellert-Miklaszewska Aleksandra, Poleszak Katarzyna, Kaminska Bozena
Laboratory of Molecular Neurobiology, Neurobiology Center, The Nencki Institute of Experimental Biology of the Polish Academy of Sciences, 3 Pasteur Str., 02-093 Warsaw, Poland.
GLIA Sp.z.o.o., Slominskiego 15/509, 00-195 Warsaw, Poland.
Future Med Chem. 2017 Jan;9(2):199-221. doi: 10.4155/fmc-2016-0189. Epub 2017 Jan 23.
Short peptides have many advantages, such as low molecular weight, selectivity for a specific target, organelles or cells with minimal toxicity. We describe properties of short peptides, which interfere with communication networks in tumor cells and within microenvironment of malignant gliomas, the most common brain tumors. We focus on ligand/receptor axes and intracellular signaling pathways critical for gliomagenesis that could be targeted with interfering peptides. We review structures and efficacy of organelle-specific and cell-penetrating peptides and describe diverse chemical modifications increasing proteolytic stability and protecting synthetic peptides against degradation. We report results of application of short peptides in glioma therapy clinical trials, their rises and falls. The most advanced examples of therapeutics such as short interfering peptides combined with cell-penetrating peptides that show good effectiveness in disease models are presented. It is foreseen that identification of peptides with better clinical properties may improve their success rates in clinical trials.
短肽具有许多优点，如分子量低、对特定靶点、细胞器或细胞具有选择性且毒性极小。我们描述了短肽的特性，这些短肽会干扰肿瘤细胞以及恶性胶质瘤（最常见的脑肿瘤）微环境中的通讯网络。我们重点关注对胶质瘤发生至关重要的配体/受体轴和细胞内信号通路，这些通路可用干扰肽进行靶向。我们综述了细胞器特异性肽和细胞穿透肽的结构与功效，并描述了多种增加蛋白水解稳定性和保护合成肽不被降解的化学修饰。我们报告了短肽在胶质瘤治疗临床试验中的应用结果、其兴衰历程。还介绍了治疗效果最先进的实例，如在疾病模型中显示出良好效果的短干扰肽与细胞穿透肽相结合的疗法。预计鉴定出具有更好临床特性的肽可能会提高它们在临床试验中的成功率。
