Pharmacology & Therapeutics ( IF 12.0 ) Pub Date : 2023-11-10 , DOI: 10.1016/j.pharmthera.2023.108559 José Brango-Vanegas 1 , Michel Lopes Leite 2 , Kamila Botelho Sampaio de Oliveira 1 , Nicolau Brito da Cunha 3 , Octávio Luiz Franco 1
During carcinogenesis, neoplastic cells accumulate mutations in genes important for cellular homeostasis, producing defective proteins. Viral infections occur when viral capsid proteins bind to the host cell receptor, allowing the virus to enter the cells. In both cases, proteins play important roles in cancer development and viral infection, so these targets can be exploited to develop alternative treatments. mRNA display technology is a very powerful tool for the development of peptides capable of acting on specific targets in neoplastic cells or on viral capsid proteins. mRNA display technology allows the selection and evolution of peptides with desired functional properties from libraries of many nucleic acid variants. Among other advantages of this technology, the use of flexizymes allows the production of peptides with unnatural amino acid residues, which can enhance the activity of these molecules. From target immobilization, peptides with greater specificity for the targets of interest are generated during the selection rounds. Herein, we will explore the use of mRNA display technology for the development of active peptides after successive rounds of selection, using proteins present in neoplastic cells and viral particles as targets.
中文翻译:
从探索癌症和病毒靶标到通过 mRNA 展示发现活性肽
在癌变过程中,肿瘤细胞在对细胞稳态很重要的基因中积累突变,产生有缺陷的蛋白质。当病毒衣壳蛋白与宿主细胞受体结合,使病毒进入细胞时,就会发生病毒感染。在这两种情况下,蛋白质在癌症发展和病毒感染中都发挥着重要作用,因此可以利用这些目标来开发替代疗法。 mRNA 展示技术是开发能够作用于肿瘤细胞中特定靶点或病毒衣壳蛋白的肽的非常强大的工具。 mRNA 展示技术允许从许多核酸变体文库中选择和进化具有所需功能特性的肽。该技术的其他优点之一是,使用灵活酶可以生产具有非天然氨基酸残基的肽,从而增强这些分子的活性。通过靶标固定,在选择过程中产生对感兴趣靶标具有更高特异性的肽。在此,我们将探索使用 mRNA 展示技术,以肿瘤细胞和病毒颗粒中存在的蛋白质为目标,经过连续几轮的选择来开发活性肽。