Faulin Tanize do Espirito Santo, Guilherme Daniel Ferreira, Silva Aldacilene Souza, Abdalla Dulcineia Saes Parra, Hering Vitor Renaux, Politi Mario José, Maranhão Andrea Queiroz
Dept. of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of Sao Paulo, Brazil.
Biotechnol Prog. 2014 Sep-Oct;30(5):1206-13. doi: 10.1002/btpr.1935. Epub 2014 Jun 12.
Experimental studies on atherosclerosis are crucial for investigating its pathophysiology, defining new therapeutic targets, and developing new drugs and diagnostic tools. Thus, many imaging markers have been developed and introduced in experimental studies. The main advantage of these new tools is that they allow the noninvasive diagnosis of atherosclerotic vascular disease. Here, we describe the cloning, expression, purification, and stabilization of a chimeric protein specifically designed to probe cells and tissues for the presence of LDL(-), a relevant marker of atherosclerosis. The DNA sequence that encodes the anti-LDL(-) scFv, previously obtained from a hybridoma secreting an anti-LDL(-) monoclonal antibody, was inserted into the bacterial vector pET-28a(+) in tandem with a DNA sequence encoding GFP. The recombinant protein was expressed in high yields in E. coli as inclusion bodies. The applicability of GFP-scFv was assessed by ELISA, which determined its affinity for LDL(-) and confocal microscopy, that showed macrophage uptake of the protein along with LDL(-). In conclusion, our data suggest that the anti-LDL(-) GFP-scFv chimeric protein could be useful in studies on atherogenesis as well as for developing diagnostic tools for atherosclerosis.
动脉粥样硬化的实验研究对于探究其病理生理学、确定新的治疗靶点以及开发新药和诊断工具至关重要。因此,在实验研究中已经开发并引入了许多成像标记物。这些新工具的主要优点是它们能够对动脉粥样硬化性血管疾病进行非侵入性诊断。在此,我们描述了一种嵌合蛋白的克隆、表达、纯化和稳定化过程,该嵌合蛋白专门设计用于探测细胞和组织中是否存在低密度脂蛋白(LDL(-)),这是动脉粥样硬化的一个相关标志物。编码抗LDL(-)单链抗体片段(scFv)的DNA序列先前从分泌抗LDL(-)单克隆抗体的杂交瘤中获得,它与编码绿色荧光蛋白(GFP)的DNA序列串联插入细菌载体pET-28a(+)中。重组蛋白在大肠杆菌中以包涵体形式高产表达。通过酶联免疫吸附测定(ELISA)评估GFP-scFv的适用性,该方法确定了其对LDL(-)的亲和力,共聚焦显微镜检查则显示该蛋白与LDL(-)一起被巨噬细胞摄取。总之,我们的数据表明,抗LDL(-) GFP-scFv嵌合蛋白可能在动脉粥样硬化发生机制的研究以及动脉粥样硬化诊断工具的开发中有用。