以多样性为导向的接产生了细胞内的自诱导物
Leila Peraro1, Zhongju Zou, Kamlesh M Makwana1
1Department of Chemistry, Tufts University , Medford, Massachusetts 02155, United States.
Journal of the American Chemical Society
|April 18, 2017
概括
研究人员开发出新的细胞透, 诱导细胞自, 这些可以通过在体外和体内清除细胞聚合物来治疗亨廷顿病.
科学领域:
- 生物化学
- 分子生物学
- 细胞生物学
背景情况:
- 自食是一种基本的细胞过程,用于降解和回收细胞组件和异物.
- 诱导自对神经退行性和传染性疾病具有治疗潜力.
- 开发能够有效调节自的细胞是一种重大挑战.
研究的目的:
- 通过以多样性为导向的接方法,设计新的,内在的细胞透性,诱导自.
- 在试验室和体内的细胞聚合物清除和诱导自的功效.
- 阐明这些新型自诱导物的活性和细胞透的结构基础.
主要方法:
- 以多样性为导向的拼接,以创建新的结构.
- 在体外测试以测量自诱导和聚合物清除活性.
- 评估自诱导的体内研究.
- 量化细胞透试验,测量细胞透.
- 解决方案结构的确定一个强大的接 (DD5-o).
主要成果:
- 以多样性为导向的接方法成功产生了细胞透的自诱导.
- 最强效的,DD5-o,在微分子度中诱导了自,并在亨廷顿病细胞模型中表现出聚合物清除活性.
- 在体内,DD5-o也诱导了自.
- 结构分析显示DD5-o采用了α-螺旋形状,由一个不寻常的 (i,i+3) 支柱稳定,其中包括d-氨基酸.
- 一个新的测量量量证实了DD5-o的细胞透.
结论:
- 使用以多样性为导向的接方法开发了新的细胞透自诱导剂.
- 这些,以DD5-o为例,在调节自和清除聚合物方面是有效的,具有治疗潜力.
- 这些发现为这些新型诱导剂的结构-活性关系提供了关键的分子见解.
- 以多样性为导向的接为增强细胞透的多离子序列提供了可行的替代方案.
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