The linear undecapeptide KKLFKKILKYL-NH2 (BP100) highlights for its antibacterial activity against Gram-negative bacteria and its low toxicity. These excellent biological properties prompted the investigation of its mechanism of action, which were undertaken using spectroscopic techniques, biophysical analysis, microscopy, and molecular dynamic simulations. Studies were conducted in different membrane environments, such as anionic, zwitterionic, and mixed membranes, as well as in vesicles (LUVs and GUVs) and bacteria. The findings suggest that BP100 exhibits a preference for anionic membranes, and its mechanism of action involves charge neutralization and membrane permeabilization. In these membranes, BP100 transitions from an unstructured state in water to an α-helix with the axis parallel to the surface. MD simulations suggest that after electrostatic interaction with the membrane, BP100 flips, facilitating the insertion of its hydrophobic face into the membrane bilayer. Thus, BP100 adopts an almost vertical transmembrane orientation with lysine side chains snorkelling on both sides of the membrane. As a result of the rotation, BP100 induces membrane thinning and slow lipid diffusion and promotes water penetration, particularly in anionic lipid membranes. These investigations pointed towards a carpet-like mechanism and are aligned with the biological activity profile described for BP100. This review covers all the studies carried out on the mechanism of action of BP100 published between 2009 and 2023.

中文翻译：

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破译抗菌肽 BP100 的作用机制

线性十一肽 KKLFKKILKYL-NH2 (BP100) 以其对革兰氏阴性菌的抗菌活性和低毒性而著称。这些优异的生物学特性促使人们利用光谱技术、生物物理分析、显微镜和分子动力学模拟对其作用机制进行研究。研究在不同的膜环境中进行，例如阴离子膜、两性离子膜和混合膜，以及囊泡（LUV 和 GUV）和细菌。研究结果表明，BP100 对阴离子膜表现出偏好，其作用机制涉及电荷中和和膜透化。在这些膜中，BP100 从水中的非结构化状态转变为轴平行于表面的 α 螺旋。MD 模拟表明，在与膜发生静电相互作用后，BP100 翻转，有利于其疏水面插入膜双层中。因此，BP100采用几乎垂直的跨膜方向，赖氨酸侧链浮潜在膜的两侧。由于旋转，BP100 会导致膜变薄、减缓脂质扩散并促进水渗透，特别是在阴离子脂质膜中。这些研究指出了类似地毯的机制，并且与 BP100 描述的生物活性特征一致。本综述涵盖了2009年至2023年间发表的所有关于BP100作用机制的研究。