Membrane Active Peptides and Their Biophysical Characterization.

Membrane Active Peptides and Their Biophysical Characterization.
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DOI:
10.3390/biom8030077
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发表时间:
2018-08-22
期刊:
影响因子:
5.5
通讯作者:
Ozkirimli E
Ozkirimli E
中科院分区:
生物学2区
文献类型:
--
作者:
Avci FG;Akbulut BS;Ozkirimli E

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在过去的20年里,越来越多的研究报道了膜活性肽。这些肽通过与细胞膜相互作用来发挥其生物活性,或者破坏细胞膜并导致细胞裂解,或者通过细胞膜转位以将货物递送到细胞中并到达其靶标。膜活性肽是目前使用的药物的有吸引力的替代品,并且在药物管道中设计用于药物和基因递送的抗菌肽(AMP)和肽的数量正在增加。在这里,我们专注于两个最突出的类膜活性肽; AMP和细胞穿透肽(CPP)。抗菌肽是一类具有破坏细胞膜完整性或抑制细菌、病毒和真菌细胞功能的膜活性肽。细胞穿透肽是另一类膜活性肽,尽管它们也可能显示出抗微生物活性,但它们主要用作货物载体。由于光学、图像处理和计算资源的进步,生物物理技术以更高的分辨率揭示了肽-膜相互作用。膜活性肽在膜存在下的结构研究提供了重要的线索,膜环境对肽构象的影响。实时成像技术允许在单细胞或单分子水平上检查肽的作用。除了这些实验生物物理技术,分子动力学模拟提供了线索的肽-脂质相互作用和动力学的细胞进入过程中的原子细节。本文综述了近年来膜活性肽的实验和计算研究进展,重点介绍了两种两亲性膜活性肽AMP蜂毒肽和CPP pVEC。
In the last 20 years, an increasing number of studies have been reported on membrane active peptides. These peptides exert their biological activity by interacting with the cell membrane, either to disrupt it and lead to cell lysis or to translocate through it to deliver cargos into the cell and reach their target. Membrane active peptides are attractive alternatives to currently used pharmaceuticals and the number of antimicrobial peptides (AMPs) and peptides designed for drug and gene delivery in the drug pipeline is increasing. Here, we focus on two most prominent classes of membrane active peptides; AMPs and cell-penetrating peptides (CPPs). Antimicrobial peptides are a group of membrane active peptides that disrupt the membrane integrity or inhibit the cellular functions of bacteria, virus, and fungi. Cell penetrating peptides are another group of membrane active peptides that mainly function as cargo-carriers even though they may also show antimicrobial activity. Biophysical techniques shed light on peptide–membrane interactions at higher resolution due to the advances in optics, image processing, and computational resources. Structural investigation of membrane active peptides in the presence of the membrane provides important clues on the effect of the membrane environment on peptide conformations. Live imaging techniques allow examination of peptide action at a single cell or single molecule level. In addition to these experimental biophysical techniques, molecular dynamics simulations provide clues on the peptide–lipid interactions and dynamics of the cell entry process at atomic detail. In this review, we summarize the recent advances in experimental and computational investigation of membrane active peptides with particular emphasis on two amphipathic membrane active peptides, the AMP melittin and the CPP pVEC.
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