摘要
天青蛋白是含有铜离子配位的蛋白质.基于天青蛋白的配位化学特点和生物学特性,将蛋白质进行改造得到了H117G突变体,使其具有结合外源咪唑和组氨酸的功能.该突变体可以用于结合具有抗癌作用的顺铂的Pt(IV)前体药物.采用紫外可见滴定等方法对蛋白质与咪唑类化合物的结合作用进行了研究,在此基础上,制备了一种新型的蛋白-药物复合物,并初步检验了该复合物对肿瘤细胞生长的抑制作用.
Azurin is a copper protein and possesses antitumor activity. The H117 G mutant of Azurin( Az-H117G)was prepared,which is capable to bind exogenous imidazole or histidine. The interaction of Az-H117 G with imidazole-based derivatives was investigated using UV-vis spectroscopy. Results show that the protein mutant can bind imidazole,histidine and Pt-His complex,a Pt( IV) prodrug of cisplatin. Based on this information,the protein / drug conjugate was prepared and the anti-proliferation of tumor cells was studied. The result indicates that this protein / drug conjugate might be potentially applicable to antitumor drug design.
基金
江苏省自然科学基金青年基金(BK20150649)资助
