靶向细胞因子CD40的全新多肽配体的筛选与鉴定  

Screening and Identification of Novel Peptide Ligand Targeting Cytokine CD40

作　　者：蓝莹莹[1,2] 丁茜[1,2] 徐宇虹[1,2] 

机构地区：[1]上海交通大学生命科学与技术学院,上海200030 [2]上海交通大学药学院,上海200030

出　　处：《生物物理学报》2014年第1期35-46,共12页Acta Biophysica Sinica

基　　金：国家自然科学基金项目(30825045)~~

摘　　要：CD40是肿瘤坏死因子受体(tumornecrosis factor receptor,TNFR)超家族成员,表达于免疫细胞、造血细胞、血管细胞、内皮细胞及多种类型的癌细胞表面。作者采用计算机虚拟筛选和细胞实验相结合的方法,研究了CD40蛋白的全新多肽配体。首先,通过同源建模构建CD40蛋白的三维结构;然后,用分子对接虚拟筛选出靶向CD40的多肽配体;再通过表面等离子体共振(surface plasmon resonance,SPR)分子结合实验、多肽靶向脂质体的细胞实验,验证并确定被命名为N9的六肽为CD40的全新配体。进一步研究发现,N9修饰的脂质体对其靶向细胞Raji和树突状细胞(dendritic cells,DC)的转染效果明显提高,提示N9有靶向介导转染的功能。CD40 is an important member of tumor necrosis factor receptor （TNFR） superfamily, expressed in immune cells, hematopoietic cells, blood cells, endothelial cells and various types of cancer cell surfaces. In this paper, the authors used computer virtual screening and cell assays for identification of the novel peptide ligands targeting CD40. First, they constructed CD40 protein three-dimensional structure by homology modeling, and conducted molecular docking with a virtual peptide library. SPR binding assay and peptide-modified liposome cells assay demonstrate that a hexapeptide named N9 is a novel CD40 ligand. In further transfection studies, N9-modified liposome was found to significantly improve the efficiency of Raji cells and dendritic cells （DC）, suggesting that N9 has capabilities to targetedly mediate the transfection.

关 键 词：CD40 多肽配体 AUTODOCK 脂质体 树突状细胞 

分 类 号：R94[医药卫生—药剂学]