...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Medicinal chemistry research: an international journal for rapid communications on design and mechanisms of action of biologically active agents >Synthesis of D-amino acid peptides and their effect on beta-amyloid aggregation and toxicity in transgenic Caenorhabditis elegans
【24h】

Synthesis of D-amino acid peptides and their effect on beta-amyloid aggregation and toxicity in transgenic Caenorhabditis elegans

机译：D-氨基酸肽的合成及其对转基因秀丽隐杆线虫中β淀粉样蛋白聚集和毒性的影响

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

Genetic, biochemical, and pathological evidence supports that aggregation of amyloid-beta (AP) peptide into fibrillar structures rich in beta-sheets is implicated as the cause of Alzheimer's disease. Therefore, an attractive therapeutic strategy is to prevent or alter amyloid-beta aggregation. In this work we examine the effects of the short D-peptides pgklvya, kklvffarrrra, and kklvffa on Abeta aggregation in vitro and toxicity in vivo. These peptides are based on the central hydrophobic region of Abeta (residues 16-20), which is believed to be crucial in Abeta self-association. The effect of peptides on Abeta aggregation was examined by circular dichroism spectroscopy, Thioflavin T fluorescence, and ANS binding assay. Transgenic Caenorhabditis elegans model was used to evaluate the pharmacological effect of D-peptides on Abeta-initiated toxicity. The data suggested that D-peptides are very effective at inhibiting fibrillogenesis of Abeta. Among the three peptides tested, only pgklvya and kklvffa improved survival in the transgenic C. elegans. The activity of these peptides correlates with their ability to inhibit Ap oligomerization. These suggest that D-peptides should be considered during future design of peptide-based inhibitors of amyloid deposition and toxicity.
机译：遗传，生物化学和病理学证据支持将淀粉样β（AP）肽聚集成富含β-折叠的纤维状结构，被认为是阿尔茨海默氏病的病因。因此，一种有吸引力的治疗策略是预防或改变淀粉样蛋白β的聚集。在这项工作中，我们研究了短D肽pgklvya，kklvffarrrra和kklvffa对Abeta体外和体内毒性的影响。这些肽基于Abeta的中央疏水区（残基16-20），据信在Abeta自缔合中至关重要。通过圆二色谱，硫黄素T荧光和ANS结合测定法检查了肽对Abeta聚集的影响。使用转基因秀丽隐杆线虫模型评估D肽对Abeta引发的毒性的药理作用。数据表明，D肽在抑制Abeta的原纤维形成方面非常有效。在测试的三种肽中，只有pgklvya和kklvffa改善了转基因秀丽隐杆线虫的存活。这些肽的活性与其抑制Aβ寡聚化的能力有关。这些提示，在未来设计基于肽的淀粉样蛋白沉积和毒性抑制剂时，应考虑使用D肽。

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