Translocation of molecules into cells by pH-dependent insertion of a transmembrane helix
Translocation of molecules into cells by pH-dependent insertion of a transmembrane helix
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DOI：
10.1073/pnas.0601463103
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发表时间：
2006-04-25
影响因子：
11.1
通讯作者：
Engelman, DM
中科院分区：
文献类型：
--
作者：
Reshetnyak, YK;Andreev, OA;Engelman, DM
我们先前已经观察到水溶性肽的自发的pH依赖性插入以形成穿过脂质双层的螺旋[Hunt，J.F.，拉特，P.，Rothschild，K. J. & Engelman，D. M.（1997）Biochemistry 36，15177-15192]。我们现在使用一种相关的肽，pH（低）插入肽，将附着在其C末端的货物分子转运穿过活细胞的质膜。易位对于低pH是选择性的，并且通过二硫化物连接的各种类型的货物分子可以通过在细胞质中还原而释放，包括肽核酸、环肽（鬼笔环肽）和有机化合物。因为高细胞外酸度是多种病理状况（如肿瘤、梗塞、中风折磨的组织、动脉粥样硬化病变、炎症或感染部位、或由创伤引起的受损组织）的特征，或者可能是人工产生的，所以pH（低）插入肽可以证明是用于选择性递送药物治疗、诊断成像、遗传控制或细胞调节的试剂的有用工具。
We have previously observed the spontaneous, pH-dependent insertion of a water-soluble peptide to form a helix across lipid bilayers [Hunt, J. F., Rath, P., Rothschild, K. J. & Engelman, D. M. (1997) Biochemistry 36, 15177-15192]. We now use a related peptide, pH (low) insertion peptide, to translocate cargo molecules attached to its C terminus across the plasma membranes of living cells. Translocation is selective for low pH, and various types of cargo molecules attached by disulfides can be released by reduction in the cytoplasm, including peptide nucleic acids, a cyclic peptide (phalloidin), and organic compounds. Because a high extracellular acidity is characteristic of a variety of pathological conditions (such as tumors, infarcts, stroke-afflicted tissue, atherosclerotic lesions, sites of inflammation or infection, or damaged tissue resulting from trauma) or might be created artificially, pH (low) insertion peptide may prove a useful tool for selective delivery of agents for drug therapy, diagnostic imaging, genetic control, or cell regulation.