• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Life sciences >Uncharged thioflavin-T derivatives bind to amyloid-beta protein with high affinity and readily enter the brain.
【24h】

Uncharged thioflavin-T derivatives bind to amyloid-beta protein with high affinity and readily enter the brain.

机译：不带电荷的硫磺黄素-T衍生物以高亲和力与淀粉样β蛋白结合，并易于进入大脑。

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

In vivo assessment of the beta-sheet proteins deposited in amyloid plaques (A beta peptide) or neurofibrillary tangles (tau protein) presents a target for the development of biological markers for Alzheimer's disease (AD). In an effort to develop in vivo beta-sheet imaging probes, derivatives of thioflavin-T (ThT) were synthesized and evaluated. These compounds lack the positively charged quaternary heterocyclic nitrogen of ThT and are therefore uncharged at physiological pH. They are 600-fold more lipophilic than ThT. These ThT derivatives bind to A beta(1-40) fibrils with higher affinity (Ki = 20.2 nM) than ThT (Ki = 890 nM). The uncharged ThT derivatives stained both plaques and neurofibrillary tangles in post-mortem AD brain, showing some preference for plaque staining. A carbon-11 labeled compound, [N-methyl-11C]6-Me-BTA-1, was prepared, and its brain entry and clearance were studied in Swiss-Webster mice. This compound entered the brain at levels comparable to commonly used neuroreceptor imaging agents (0.223 %ID-kg/g or 7.61 %ID/g at 2 min post-injection) and showed good clearance of free and non-specifically bound radioactivity in normal rodent brain tissue (brain clearance t(1,2) = 20 min). The combination of relatively high affinity for amyloid, specificity for staining plaques and neurofibrillary tangles in post-mortem AD brain, and good brain entry and clearance makes [N-methyl-11C]6-Me-BTA-1 a promising candidate as an in vivo positron emission tomography (PET) beta-sheet imaging agent.
机译：体内评估沉积在淀粉样蛋白斑块（Aβ肽）或神经原纤维缠结（Tau蛋白）中的β-折叠蛋白为开发阿尔茨海默氏病（AD）生物学标记物提供了目标。为了开发体内β-折叠成像探针，合成并评估了硫黄素-T（ThT）的衍生物。这些化合物缺少ThT带正电的季杂环氮，因此在生理pH值不带电。它们的亲脂性比ThT高600倍。这些ThT衍生物以比ThT（Ki = 890 nM）更高的亲和力（Ki = 20.2 nM）与A beta（1-40）原纤维结合。不带电的ThT衍生物在验尸AD脑中同时染色斑块和神经原纤维缠结，显示出对斑块染色的偏爱。制备了碳11标记的化合物[N-甲基-11C] 6-Me-BTA-1，并在Swiss-Webster小鼠中研究了其脑进入和清除。该化合物以与常用神经受体显像剂相当的水平（注射后2分钟时为0.223％ID-kg / g或7.61％ID / g）进入大脑，并在正常啮齿动物中表现出良好的游离和非特异性结合放射性清除率脑组织（大脑清除率t（1,2）= 20分钟）。对淀粉样蛋白相对较高的亲和力，验尸后AD大脑中斑块和神经原纤维缠结的特异性以及良好的大脑进入和清除能力相结合，使得[N-methyl-11C] 6-Me-BTA-1成为有希望的候选药物。体内正电子发射断层扫描（PET）β-sheet成像剂。

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