Drug Targeting Based on a New Concept-Targeting Against TLR4 as an Example.
Drug Targeting Based on a New Concept-Targeting Against TLR4 as an Example.
复制标题
DOI：
10.2174/187153031502150522123746
复制
发表时间：
2015-05
期刊：
影响因子：
--
通讯作者：
Y. Maru;T. Tomita;A. Deguchi;Katsuaki Ieguchi;M. Takita;F. Tsukahara;Kazuhiro Takemura;A. Kitao;F. Gusovsky
中科院分区：
文献类型：
--
作者：
Y. Maru;T. Tomita;A. Deguchi;Katsuaki Ieguchi;M. Takita;F. Tsukahara;Kazuhiro Takemura;A. Kitao;F. Gusovsky
TLR是调节先天性免疫应答的非常重要的参与者。TLR 4通过感知外来病原体（如脂多糖）来控制宿主防御。同时，一些内源性蛋白，包括HMGB 1和S100 A8，也可以作为一个配体，引发炎症反应。这些事实使得TLR 4信号系统非常复杂。例如，TLR 4配体在癌症治疗中的应用就其修复性质而言对于增强抗肿瘤免疫是期望的，但对于增强癌细胞的转移性生长是不期望的。在这篇文章中，为了进行一种新的分子设计来破坏TLR 4/MD-2和内源性配体之间的相互作用，我们提供了一个潜在的结合方式TLR 4/MD-2复合物与HMGB 1通过使用它们的三维结构数据和对接模拟，并讨论S100 A8与TLR 4/MD-2的结合。
TLRs are very important players to regulate innate immune responses. TLR4 controls the host defense by sensing an exotic pathogen, such as lipopolysaccharides. At the same time, some endogenous proteins, including HMGB1 and S100A8, could also function to be a ligand to elicit inflammatory reactions. These facts make TLR4 signaling system very complicated. For instance, the application of TLR4 ligands in cancer therapies is desirable for enhancement of anti-tumor immunity in terms of its reparative nature, but undesirable for enhancement of metastatic growth of cancer cells. In this manuscript, in order to make a novel molecular design to disrupt an interaction between TLR4/MD-2 and endogenous ligands, we provide a potential binding style of the TLR4/MD-2 complex with HMGB1 by using their 3D structural data and docking simulations, and also discuss S100A8 binding to TLR4/MD-2.