Tat-Mediated Peptide Intervention in Analgesia and Anesthesia.
Tat-Mediated Peptide Intervention in Analgesia and Anesthesia.
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DOI：
10.1002/ddr.20331
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发表时间：
2010-04-01
影响因子：
3.8
通讯作者：
Johns, Roger A.
中科院分区：
文献类型：
--
作者：
Tao, Feng;Johns, Roger A.
关键词：
膜渗透性多肽载体是很有吸引力的药物递送工具。在这些载体中，人类免疫缺陷病毒1型Tat蛋白的蛋白质转导结构域（PTD）是最常用的，并已成功地证明可以运送各种各样的货物。Tat PTD可以促进大型生物活性分子进入哺乳动物细胞的吸收，最近的研究表明，它可以介导不同货物进入整个生物体的组织。鉴于Tat ptd介导的递送与大小无关，该技术可以使以前不适用的大分子可用于调节体内生物功能和治疗人类疾病。肽载体介导的细胞内递送过程可能包含多种机制，但内吞途径是主要的内化途径。PTD已成功应用于癌症、缺血、炎症、镇痛和麻醉的临床前模型研究。我们最近的研究表明，腹腔注射融合肽Tat-PSD-95 PDZ2可以被递送到脊髓中，以剂量依赖性地破坏PSD-95和NMDA受体之间的蛋白-蛋白相互作用。这种肽显著抑制慢性炎症性疼痛，降低氟烷麻醉的阈值。Tat PTD靶向任何细胞的能力在某些方面是有利的。然而，如果我们可以修改Tat PTD，使其只将货物输送到所需的器官，以避免可能的副作用，那么药物输送系统将更具吸引力。
Membrane-permeable peptide carriers are attractive drug delivery tools. Among such carriers, the protein transduction domain (PTD) of the human immunodeficiency virus-type 1 Tat protein is most frequently used and has been successfully shown to deliver a large variety of cargoes. The Tat PTD can facilitate the uptake of large, biologically active molecules into mammalian cells, and recent studies have shown that it can mediate the delivery of different cargoes into tissues throughout a living organism. Given that the Tat PTD-mediated delivery is size-independent, this technology could make previously non-applicable large molecules usable to modulate biological function in vivo and treat human diseases. It is likely that the peptide carrier-mediated intracellular delivery process encompasses multiple mechanisms, but endocytic pathways are the predominant internalization routes. Tat PTD has been successfully used in preclinical models for the study of cancer, ischemia, inflammation, analgesia, and anesthesia. Our recent studies have shown that intraperitoneally injected fusion Tat peptide Tat-PSD-95 PDZ2 can be delivered into the spinal cord to dose-dependently disrupt protein-protein interactions between PSD-95 and NMDA receptors. This peptide significantly inhibits chronic inflammatory pain and reduces the threshold for halothane anesthesia. The ability of the Tat PTD to target any cell is advantageous in some respects. However, the drug delivery system will be more attractive if we can modify the Tat PTD to deliver cargo only into desired organs to avoid possible side effects.
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影响因子：
3.9
作者：
Futaki, S.;Nakase, I.;Jones, A. T.
通讯作者：
Jones, A. T.
DOI：
10.1016/j.bbrc.2008.04.039
发表时间：
2008-07-11
影响因子：
3.1
作者：
Amand, Helene L.;Fant, Kristina;Esbjorner, Elin K.
通讯作者：
Esbjorner, Elin K.
影响因子：
4.6
作者：
Cai, SR;Xu, G;McLeod, HL
通讯作者：
McLeod, HL
影响因子：
4.8
作者：
Christopherson, KS;Hillier, BJ;Bredt, DS
通讯作者：
Bredt, DS
影响因子：
1.7
作者：
Garry, MG;Malik, S;Yang, J
通讯作者：
Yang, J