Papo Niv, Shai Yechiel
Department of Biological Chemistry, The Weizmann Institute of Science, Herzel Street, Rehovot 76100, Israel.
Peptides. 2003 Nov;24(11):1693-703. doi: 10.1016/j.peptides.2003.09.013.
Cationic antibacterial peptides are produced in all living organisms and possess either selective activity toward a certain type of cell or microorganism, or a broad spectrum of activity toward several types of cells including prokaryotic and mammalian cells. In order to exert their activity, peptides first interact with and traverse an outer barrier, e.g., mainly LPS and peptidoglycan in bacteria or a glycocalix layer and matrix proteins in mammalian cells. Only then, can the peptides bind and insert into the cytoplasmic membrane. The mode of action of many antibacterial peptides is believed to be the disruption of the lipidic plasma membrane. Therefore, model phospholipid membranes have been used to study the mode of action of antimicrobial peptides. These studies have demonstrated that peptides that act preferentially on bacteria are also able to interact with and permeate efficiently anionic phospholipids, whereas peptides that lyse mammalian cells bind and permeate efficiently both acidic and zwitterionic phospholipids membranes, mimicking the plasma membranes of these cells. It is now becoming increasingly clear that selective activity of these peptides against different cells depends also on other parameters that characterize both the peptide and the target cell. With respect to the peptide's properties, these include the volume of the molecule, its structure, and its oligomeric state in solution and in membranes. Regarding the target membrane, these include the structure, length, and complexity of the hydrophilic polysaccharide found in its outer layer. These parameters affect the ability of the peptides to diffuse through the cell's outer barrier and to reach its cytoplasmic plasma membrane.
阳离子抗菌肽在所有生物中都有产生，要么对某一特定类型的细胞或微生物具有选择性活性，要么对包括原核细胞和哺乳动物细胞在内的几种类型的细胞具有广泛的活性。为了发挥其活性，肽首先与外部屏障相互作用并穿过该屏障，例如，细菌中的主要成分脂多糖和肽聚糖，或哺乳动物细胞中的糖萼层和基质蛋白。只有这样，肽才能结合并插入细胞质膜。许多抗菌肽的作用方式被认为是破坏脂质质膜。因此，模型磷脂膜已被用于研究抗菌肽的作用方式。这些研究表明，优先作用于细菌的肽也能够与阴离子磷脂相互作用并有效地渗透，而裂解哺乳动物细胞的肽则能有效地结合并渗透酸性和两性离子磷脂膜，模拟这些细胞的质膜。现在越来越清楚的是，这些肽对不同细胞的选择性活性还取决于表征肽和靶细胞的其他参数。就肽的性质而言，这些参数包括分子体积、其结构以及它在溶液和膜中的寡聚状态。关于靶膜，这些参数包括其外层中亲水性多糖的结构、长度和复杂性。这些参数影响肽扩散穿过细胞外部屏障并到达其细胞质质膜的能力。
