• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Platelets >Considerations on inhibition approaches for proinflammatory functions of ADAM proteases
【24h】

Considerations on inhibition approaches for proinflammatory functions of ADAM proteases

机译：关于ADAM蛋白酶促炎函数抑制方法的思考

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Proteases of the disintegrin and metalloproteinase (ADAM) family mediate the proteolytic shedding of various surface molecules including cytokine precursors, adhesion molecules, growth factors, and receptors. Within the vasculature ADAM10 and ADAM17 regulate endothelial permeability, transendothelial leukocyte migration, and the adhesion of leukocytes and platelets. In vivo studies show that both proteases are implicated in several inflammatory pathologies, for example, edema formation, leukocyte infiltration, and thrombosis. However, both proteases also contribute to developmental and regenerative processes. Thus, although ADAMs can be regarded as valuable drug targets in many aspects, the danger of severe side effects is clearly visible. To circumvent these side effects, traditional inhibition approaches have to be improved to target ADAMs at the right time in the right place. Moreover, the inhibitors need to be more selective for the target protease and if possible also for the substrate. Antibodies recognizing the active conformation of ADAMs or small molecules blocking exosites of ADAM proteases may represent inhibitors with the desired selectivities.
机译：去整合素和金属蛋白酶（ADAM）家族的蛋白酶介导各种表面分子的蛋白水解脱落，包括细胞因子前体、粘附分子、生长因子和受体。在血管系统内，ADAM10和ADAM17调节内皮通透性、白细胞跨内皮迁移以及白细胞和血小板的粘附。体内研究表明，这两种蛋白酶都与几种炎症病理有关，例如水肿形成、白细胞浸润和血栓形成。然而，这两种蛋白酶也有助于发育和再生过程。因此，尽管亚当斯在许多方面都可以被视为有价值的药物靶点，但严重副作用的危险是显而易见的。为了避免这些副作用，必须改进传统的抑制方法，以便在正确的时间、正确的地点针对ADAMs。此外，抑制剂需要对目标蛋白酶具有更高的选择性，如果可能的话，还需要对底物具有更高的选择性。识别ADAMs活性构象的抗体或阻断ADAMs蛋白酶外位点的小分子可能代表具有所需选择性的抑制剂。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号