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高温下产生的骆驼乳白蛋白与不饱和脂肪酸细胞毒性复合物的结构与稳定性分析。

Structure and stability analysis of cytotoxic complex of camel α-lactalbumin and unsaturated fatty acids produced at high temperature.

机构信息

Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.

出版信息

J Biomol Struct Dyn. 2011 Jun;28(6):919-28. doi: 10.1080/07391102.2011.10508618.

Abstract

α-Lactalbumin α-La), together with oleic acid can be converted to a complex, which kills tumor cells selectively. Cytotoxic α-La -oleic acid and α-La -linoleic acid complexes were generated by adding fatty acid to camel holo α-La at 60 ° C (referred to as La-OA-60 and La-LA-60 state, respectively). Structural properties of these complexes were studied and compared to the camel α-La. The experimental results show that linoleic acid induces α-La partial unfolding but oleic acid does not change the protein structure significantly. Also the stability of La-OA-60 and La-LA-60 toward thermal denaturation was measured. The order of temperature at the transition midpoint is as follows: La-LA-60 < La-OA-60 < α-La. La-OA-60 complex inhibited tubulin polymerization in vitro. Although the structures of La-OA-60 and La-LA-60 were different, these two complexes had similar cytotoxic effect to DU145 human prostate cancer cells. Samples of La-OA-60 that have been renatured after denaturation lost the specific biological activity toward tumor cells.

摘要

α-乳白蛋白(α-La)与油酸结合可转化为一种复合物,这种复合物可选择性地杀死肿瘤细胞。通过在 60°C 时向骆驼全α-La 中添加脂肪酸,可生成具有细胞毒性的α-La-油酸和α-La-亚油酸复合物(分别称为 La-OA-60 和 La-LA-60 态)。研究了这些复合物的结构特性,并与骆驼α-La 进行了比较。实验结果表明,亚油酸诱导α-La 部分展开,但油酸对蛋白质结构没有明显影响。还测量了 La-OA-60 和 La-LA-60 对热变性的稳定性。转变中点温度的顺序如下:La-LA-60<La-OA-60<α-La。La-OA-60 复合物在体外抑制微管蛋白聚合。尽管 La-OA-60 和 La-LA-60 的结构不同,但这两种复合物对 DU145 人前列腺癌细胞均具有相似的细胞毒性作用。复性后变性的 La-OA-60 样品丧失了对肿瘤细胞的特异性生物活性。

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