Targeting diseased tissues by pHLIP insertion at low cell surface pH.
Targeting diseased tissues by pHLIP insertion at low cell surface pH.
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DOI：
10.3389/fphys.2014.00097
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发表时间：
2014
影响因子：
4
通讯作者：
Reshetnyak YK
中科院分区：
文献类型：
--
作者：
Andreev OA;Engelman DM;Reshetnyak YK
PH低插入多肽(PHLIPs®)的发现为开发针对胞外酸性的成像和药物递送剂提供了机会。细胞外酸性与许多病理状态有关，如癌症、缺血性中风、神经创伤、感染、撕裂伤等。损伤或病变组织中细胞的代谢经常导致细胞外环境的酸化，因此，如果能够开发一种有效的靶向方法，酸中毒可能成为疾病状态成像和治疗的通用标志。PHLIP多肽的分子机制是基于pH依赖的膜相关折叠。PHLIP是一种中等疏水性的多肽，在正常pH下对细胞膜有很高的亲和力，但在低pH时折叠并跨膜插入，使它们能够感觉到病变组织中细胞表面的pH，那里是最低的。在此，我们讨论了PHLIP在中性和低pH下与膜脂双层相互作用的主要原理，通过改变多肽序列来调节折叠和插入pH的可能性，以及PHLIP在成像、治疗和图像引导干预方面的潜在应用。
The discovery of the pH Low Insertion Peptides (pHLIPs®) provides an opportunity to develop imaging and drug delivery agents targeting extracellular acidity. Extracellular acidity is associated with many pathological states, such as those in cancer, ischemic stroke, neurotrauma, infection, lacerations, and others. The metabolism of cells in injured or diseased tissues often results in the acidification of the extracellular environment, so acidosis might be useful as a general marker for the imaging and treatment of diseased states if an effective targeting method can be developed. The molecular mechanism of a pHLIP peptide is based on pH-dependent membrane-associated folding. pHLIPs, being moderately hydrophobic peptides, have high affinities for cellular membranes at normal pH, but fold and insert across membranes at low pH, allowing them to sense pH at the surfaces of cells in diseased tissues, where it is the lowest. Here we discuss the main principles of pHLIP interactions with membrane lipid bilayers at neutral and low pHs, the possibility of tuning the folding and insertion pH by peptide sequence variation, and potential applications of pHLIPs for imaging, therapy and image-guided interventions.
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影响因子：
3.1
作者：
Li N;Yin L;Thévenin D;Yamada Y;Limmon G;Chen J;Chow VT;Engelman DM;Engelward BP
通讯作者：
Engelward BP
影响因子：
5.6
作者：
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通讯作者：
Engelman, Donald M.
影响因子：
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作者：
Hashim, Arig Ibrahim;Zhang, Xiaomeng;Wojtkowiak, Jonathan W.;Martinez, Gary V.;Gillies, Robert J.
通讯作者：
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DOI：
10.1073/pnas.0914330107
发表时间：
2010-03-02
影响因子：
11.1
作者：
Andreev, Oleg A.;Karabadzhak, Alexander G.;Reshetnyak, Yana K.
通讯作者：
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DOI：
10.1016/j.biocel.2007.03.021
发表时间：
2007-01-01
影响因子：
4
作者：
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通讯作者：
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