通过合成演化的pH触发,大分子大小的脂质分片
Gregory Wiedman1,2, Sarah Y Kim3,2, Elmer Zapata-Mercado3,2
1Department of Materials Science and Engineering, Johns Hopkins University , Baltimore, Maryland 21218, United States.
Journal of the American Chemical Society
|December 22, 2016
概括
研究人员开发了pH触发的,在酸性pH下形成膜中的大孔. 通过选择性透癌细胞膜,这些具有向药物输送和癌症治疗的潜力.
科学领域:
- 生物化学
- 分子生物学
- 材料科学
背景情况:
- 在细胞输送和癌症治疗中具有潜在的应用.
- 一个关键的挑战是开发可以促进大分子跨膜的运输的,这种特性在现有的膜透中很少见.
研究的目的:
- 识别具有双重性质的新序列:在生理pH (7.0) 时最小的膜透,在酸性pH (5.0) 时有效形成大分子大小的缺陷.
- 探索这些在需要pH特异性膜破坏的应用中的潜力,例如向药物输送和癌症治疗.
主要方法:
- 使用代库采用直角高通量选方法.
- 根据它们在酸性pH (5.0) 时形成大分子大小的毛孔的能力而选择,而在生理pH (7.0) 时表现出低活性.
主要成果:
- 选择的体在pH值为5. 0时表现出强烈的宏分子大小的孔隙形成,在pH值为7. 0时具有微不足道的活性.
- 的活性可能由膜分离,α螺旋形成和静电相互作用的组合来控制,导致pH激发的过渡.
- 这种转变的明显pKa值被确定为5. 5至5. 8.
结论:
- 该研究成功地确定了高效的pH触发型,大分子大小的孔形成.
- 这些具有精确的pH依赖活性,使其成为细胞传递和向癌症治疗中先进应用的有希望的候选者.
- 这项研究为开发利用生理相关的pH值变化的新基策略开辟了道路.
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