Anti-cancer activity of targeted pro-apoptotic peptides
Anti-cancer activity of targeted pro-apoptotic peptides
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DOI：
10.1038/12469
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发表时间：
1999-09-01
期刊：
影响因子：
82.9
通讯作者：
Pasqualini, R
中科院分区：
文献类型：
--
作者：
Ellerby, HM;Arap, W;Pasqualini, R
我们设计了由两个功能域组成的短肽，一个是肿瘤血管“归巢”基序，另一个是程序性细胞死亡诱导序列，并通过简单的肽化学合成了它们。“归巢”结构域被设计用于引导肽到目标细胞并允许其内化。促凋亡结构域被设计成在细胞外无毒，但通过破坏线粒体膜被内化到靶细胞时是有毒的。虽然我们的原型只含有21和26个残基，但它们对血管生成内皮细胞具有选择性毒性，并在小鼠中显示出抗癌活性。这种方法可能产生新的治疗剂。
We have designed short peptides composed of two functional domains, one a tumor blood vessel 'homing' motif and the other a programmed cell death-inducing sequence, and synthesized them by simple peptide chemistry. The 'homing' domain was designed to guide the peptide to targeted cells and allow its internalization. The pro-apoptotic domain was designed to be nontoxic outside cells, but toxic when internalized into targeted cells by the disruption of mitochondrial membranes. Although our prototypes contain only 21 and 26 residues, they were selectively toxic to angiogenic endothelial cells and showed anti-cancer activity in mice. This approach may yield new therapeutic agents.