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Effect of Helical Kink on Peptide Translocation across Phospholipid Membranes.
The Journal of Physical Chemistry B ( IF 3.3 ) Pub Date : 2020-06-30 , DOI: 10.1021/acs.jpcb.0c03291
Radim Brožek 1, 2 , Ivo Kabelka 1, 2 , Robert Vácha 1, 2, 3
Affiliation  

Biological membranes present a major obstacle for the delivery of therapeutic agents into cells. Some peptides have been shown to translocate across the membrane spontaneously, and they could be thus used as drug-carriers. However, the advantageous peptide properties for the translocation remain unclear. Of particular interest is the effect of a proline-induced kink in α-helical peptides, because the kink was previously reported to both increase and decrease the antimicrobial activity. The antimicrobial activity of peptides could be related to their translocation across the membrane as is the case of the buforin 2 peptide investigated here. Using computer simulations with two independent models, we consistently showed that the presence of the kink has (1) no effect on the translocation barrier, (2) reduces the peptide affinity to the membrane, and (3) disfavors the transmembrane state. Moreover, we were able to determine that these effects are mainly caused by the peptide increased polarity, not the increased flexibility of the kink. The provided molecular understanding can be utilized for the design of cell-penetrating and drug-carrying peptides.

中文翻译:

螺旋扭结对跨磷脂膜的肽转运的影响。

生物膜是将治疗剂输送到细胞中的主要障碍。已经显示一些肽自发地跨膜转运,因此可以用作药物载体。然而,对于易位的有利肽性质仍然不清楚。特别令人感兴趣的是脯氨酸诱导的α-螺旋肽中的扭结的作用,因为先前已报道扭结既增加又降低了抗菌活性。肽的抗菌活性可能与其在整个膜上的转运有关,就像这里研究的buforin 2肽一样。通过使用具有两个独立模型的计算机模拟,我们一致地表明纽结的存在(1)对转运屏障没有影响,(2)降低了肽对膜的亲和力,(3)不利于跨膜状态。此外,我们能够确定这些影响主要是由肽极性增加引起的,而不是扭结的柔性增加引起的。所提供的分子理解可以用于细胞穿透和载药肽的设计。
更新日期:2020-07-16
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