Synthesis and anti-cancer activity of covalent conjugates of artemisinin and a transferrin-receptor targeting peptide
Synthesis and anti-cancer activity of covalent conjugates of artemisinin and a transferrin-receptor targeting peptide
复制标题
DOI：
10.1016/j.canlet.2008.08.031
复制
发表时间：
2009-02-08
期刊：
影响因子：
9.7
通讯作者：
Sasaki, Tomikazu
中科院分区：
文献类型：
--
作者：
Oh, Steve;Kim, Byung Ju;Sasaki, Tomikazu
青蒿素是从黄花蒿中提取的天然产物，通过铁依赖性机制显示出独特的抗癌活性。青蒿素与转铁蛋白受体靶向肽HAIYPRH共价偶联，HAIYPRH与转铁蛋白受体表面的空腔结合。这使得青蒿素能够与受体结合的转铁蛋白共同内化。转铁蛋白释放的铁可以激活青蒿素，产生毒性自由基，杀死细胞。青蒿素-肽缀合物显示出对Molt-4白血病细胞的有效抗癌活性，具有显著改善的癌/正常细胞选择性。(c)2008爱思唯尔爱尔兰有限公司保留所有权利。
Artemisinin, a natural product isolated from Artemisia annua L., shows a unique anti-cancer activity by an iron dependent mechanism. Artemisinin was covalenty conjugated to a transferrin-receptor targeting peptide, HAIYPRH that binds to a cavity on the Surface Of transferrin receptor. This enables artemisinin to lie co-internalized with receptor-bound transferrin. The iron released from transferrin can activate artemisinin to generate toxic radical species to kill cells. The artemisinin-peptide conjugates showed potent anti-cancer activity against Molt-4 leukemia cells with a significantly improved cancer/normal cells selectivity. (c) 2008 Elsevier Ireland Ltd. All rights reserved.