特异性结合血管内皮生长因子受体2的融合毒素  

Vascular Endothelial Growth Factor Receptor Binding Fusion Toxin

作　　者：白向阳[1] 吴静怡[1] 孙静[2] 马丁[1] 吕安国[2] 

机构地区：[1]华中科技大学同济医学院附属同济医院肿瘤生物医学中心,武汉430030 [2]中国科学院沈阳应用生态研究所,沈阳110016

出　　处：《华中科技大学学报（医学版）》2005年第5期521-524,共4页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：国家"973"计划资助项目(No.2002CB513100)

摘　　要：目的制备特异性结合血管内皮生长因子受体2(vascular endothelial growth factor receptor-2,VEGFR-2)的融合蛋白,阻断新生肿瘤血管内皮细胞和某些VEGFR-2阳性肿瘤细胞内的蛋白合成,引起细胞死亡。方法运用基因定点突变技术,制成VEGF D63A、E64A、E67A突变体。利用这个可以和VEGFR-2特异性结合的VEGF突变体,代替白喉毒素上的受体结合区,制成了特异性结合VEGFR-2的融合蛋白。结果以去除了受体结合区的DT391作为对照,以VEGFR-2阳性肿瘤细胞做实验,验证了这个融合毒素对VEGFR-2阳性细胞的选择性杀伤作用。结论制备了特异性杀伤血管内皮生长因子受体2阳性细胞的融合毒素。Objective To prepare a fusion protein that binds specifically to vascular endothelial growth factor receptor-2 （VEGFR-2） and kills vascular endothelial cells and some VEGFR-2 positive tumor cells by blocking the protein synthesis. Methods Site-directed mutations were introduced into VEGF gene to make a VEGF D63A, E64A, E67A mutant. The mutant gene was conjugated to diphtheria toxin encoding gene to make a fusion protein that had both the VEGFR-2 binding ability and cytotoxicity of DT. Results Using DT391 as a negative control, the bioactivity of the fusion protein on cell line bearing VEGFR-2 on its surface was tested. The specific cytotoxicity was proved by VEGR-2 positive cells. Conclusion A VEGFR-2 positive cell killing protein was made.

关 键 词：白喉毒素 血管内皮生长因子 血管内皮生长因子受体 融合毒素 

分 类 号：R392.11[医药卫生—免疫学]