含有酒精的蛋白质转导域模仿了含酒精的蛋白质转导域
Kayla C Koch1, Tamara M Bizmark2, Gregory N Tew3
1Department of Polymer Science & Engineering, University of Massachusetts, Amherst, MA 01003, United States.
概括
这项研究引入了新型合成蛋白质转导域模拟器 (PTDM) 与酒精组,以增强生物宏分子的传递. 一种PTDM (PTDM4) 显著改善了抗体递送和酶活性,降低了阴离子密度.
科学领域:
- 生物技术和生物材料科学 生物技术和生物材料科学
- 聚合物化学 聚合物化学
- 药物输送系统 药物输送系统
背景情况:
- 蛋白质转导域 (PTD) 和仿真 (PTDM) 对于细胞内生物大分子的传递至关重要.
- 之前的工作是使用环开放元解聚合 (ROMP) 合成区块共聚合物PTDM,优化疏水性和离子密度.
- 自然存在的PTD含有酒精组,但它们对合成PTDM的影响尚未被探索.
研究的目的:
- 调查将酒精组纳入合成PTDMs作为新设计参数的效果.
- 合成和评估具有不同酒精组结构的新型PTDM库.
- 评估这些新型PTDM在抗体和活性酶的细胞内传递中的效率.
主要方法:
- 通过ROMP合成了9种新型PTDM,其中包含酒精组.
- 评估PTDM用于光标记抗体的细胞内传递.
- 将传递效率和阴离子密度与以前建立的PTDM控制器进行比较.
- 使用主要PTDM候选物的活性酶 (TAT-Cre重组酶) 输送和活性的评估.
主要成果:
- 一种新型PTDM,PTDM4,在疏水和阴离子块中结合了酒精组,证明了卓越的性能.
- 与对照组相比,PTDM4的抗体输送中位数光强度几乎是抗体输送的两倍.
- 为了有效的输送,PTDM4只需要控制器的一半的阴离子密度.
- 通过PTDM4释放的TAT-Cre重组酶的活性与对照组相当,也只有半个阴离子密度.
结论:
- 纳入酒精组是设计先进PTDM的可行和有效策略.
- PTDM4代表了PTDM的重大进步,提供了更高的交付效率和更低的电荷密度.
- 这项研究为优化合成PTDM用于各种细胞内输送应用开辟了新的途径.
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