靶向促凋亡肽的抗癌活性

Anti-cancer activity of targeted pro-apoptotic peptides.

作者信息

Ellerby H M, Arap W, Ellerby L M, Kain R, Andrusiak R, Rio G D, Krajewski S, Lombardo C R, Rao R, Ruoslahti E, Bredesen D E, Pasqualini R

机构信息

Program on Aging and Cancer and Program on Cell Adhesion, The Burnham Institute, 10901 North Torrey Pines Rd., La Jolla, California 92037, USA.

出版信息

Nat Med. 1999 Sep;5(9):1032-8. doi: 10.1038/12469.

DOI:10.1038/12469

PMID:10470080

Abstract

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.

摘要

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，另一个是诱导程序性细胞死亡的序列，并通过简单的肽化学方法合成了它们。“归巢”结构域旨在引导肽靶向细胞并使其内化。促凋亡结构域设计为在细胞外无毒，但通过破坏线粒体膜内化到靶向细胞时有毒。尽管我们的原型仅包含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。这种方法可能会产生新的治疗药物。