Röckendorf Niels, Nehls Christian, Gutsmann Thomas
Division of Mucosal Immunology and Diagnostics, Research Center Borstel-Leibniz Lung Center, Priority Area Chronic Lung Diseases, Member of the Airway Research Center North (ARCN), German Center for Lung Research (DZL), Parkallee 22, 23845 Borstel, Germany.
Division of Biophysics, Research Center Borstel-Leibniz Lung Center, Priority Area Infection, Parkallee 10, 23845 Borstel, Germany.
Membranes (Basel). 2022 Feb 2;12(2):180. doi: 10.3390/membranes12020180.
A multitude of membrane active peptides exists that divides into subclasses, such as cell penetrating peptides (CPPs) capable to enter eukaryotic cells or antimicrobial peptides (AMPs) able to interact with prokaryotic cell envelops. Peptide membrane interactions arise from unique sequence motifs of the peptides that account for particular physicochemical properties. Membrane active peptides are mainly cationic, often primary or secondary amphipathic, and they interact with membranes depending on the composition of the bilayer lipids. Sequences of these peptides consist of short 5-30 amino acid sections derived from natural proteins or synthetic sources. Membrane active peptides can be designed using computational methods or can be identified in screenings of combinatorial libraries. This review focuses on strategies that were successfully applied to the design and optimization of membrane active peptides with respect to the fact that diverse features of successful peptide candidates are prerequisites for biomedical application. Not only membrane activity but also degradation stability in biological environments, propensity to induce resistances, and advantageous toxicological properties are crucial parameters that have to be considered in attempts to design useful membrane active peptides. Reliable assay systems to access the different biological characteristics of numerous membrane active peptides are essential tools for multi-objective peptide optimization.
存在多种膜活性肽，它们可分为不同的亚类，例如能够进入真核细胞的细胞穿透肽（CPPs）或能够与原核细胞膜相互作用的抗菌肽（AMPs）。肽与膜的相互作用源于肽的独特序列基序，这些基序决定了特定的物理化学性质。膜活性肽主要是阳离子性的，通常是一级或二级两亲性的，它们根据双层脂质的组成与膜相互作用。这些肽的序列由源自天然蛋白质或合成来源的5 - 30个氨基酸的短片段组成。膜活性肽可以使用计算方法进行设计，也可以在组合文库筛选中鉴定。本综述重点关注已成功应用于膜活性肽设计和优化的策略，因为成功的肽候选物的多种特性是生物医学应用的先决条件。不仅膜活性，而且在生物环境中的降解稳定性、诱导抗性的倾向以及有利的毒理学特性都是在设计有用的膜活性肽时必须考虑的关键参数。用于评估众多膜活性肽不同生物学特性的可靠检测系统是多目标肽优化的重要工具。
