Renewable Product Technology Research Unit, National Center for Agricultural Utilization Research (NCAUR), Agricultural Research Service (ARS), United States Department of Agriculture (USDA), 1815 North University Street, Peoria, IL 61604, USA.
Pharmaceuticals (Basel). 2012 Sep 28;5(10):1054-63. doi: 10.3390/ph5101054.
Several important areas of interest intersect in a class of peptides characterized by their highly cationic and partly hydrophobic structure. These molecules have been called cell-penetrating peptides (CPPs) because they possess the ability to translocate across cell membranes. This ability makes these peptides attractive candidates for delivery of therapeutic compounds, especially to the interior of cells. Compounds with characteristics similar to CPPs and that, in addition, have antimicrobial properties are being investigated as antibiotics with a reduced risk of causing resistance. These CPP-like membrane-acting antimicrobial peptides (MAMPs) are α-helical amphipathic peptides that interact with and perturb cell membranes to produce their antimicrobial effects. One source of MAMPs is spider venom. Because these compounds are toxic to insects, they also show promise for development as biological agents for control of insecticide-resistant agricultural pests. Spider venom is a potential source of novel insect-specific peptide toxins. One example is the small amphipathic α-helical peptide lycotoxin-1 (Lyt-1 or LCTX) from the wolf spider (Lycosa carolinensis). One side of the α-helix has mostly hydrophilic and the other mainly hydrophobic amino acid residues. The positive charge of the hydrophilic side interacts with negatively charged prokaryotic membranes and the hydrophobic side associates with the membrane lipid bilayer to permeabilize it. Because the surface of the exoskeleton, or cuticle, of an insect is highly hydrophobic, to repel water and dirt, it would be expected that amphipathic compounds could permeabilize it. Mutagenized lycotoxin 1 peptides were produced and expressed in yeast cultures that were fed to fall armyworm (Spodoptera frugiperda) larvae to identify the most lethal mutants. Transgenic expression of spider venom toxins such as lycotoxin-1 in plants could provide durable insect resistance.
一类具有高度阳离子性和部分疏水性结构的肽，其多个重要研究领域相交。这些分子被称为细胞穿透肽（CPPs），因为它们具有穿过细胞膜的能力。这种能力使这些肽成为治疗化合物传递的有吸引力的候选物，特别是递送到细胞内部。具有类似于 CPP 特性的化合物，并且另外具有抗菌特性，正在作为具有降低耐药风险的抗生素进行研究。这些类似 CPP 的膜作用抗菌肽（MAMPs）是与细胞膜相互作用并扰乱细胞膜以产生其抗菌作用的α-螺旋两性肽。MAMPs 的一个来源是蜘蛛毒液。由于这些化合物对昆虫有毒，因此它们也有望作为生物制剂开发，用于控制对杀虫剂具有抗性的农业害虫。蜘蛛毒液是新型昆虫特异性肽毒素的潜在来源。一个例子是来自狼蛛（Lycosa carolinensis）的小两性α-螺旋肽 lycotoxin-1（Lyt-1 或 LCTX）。α-螺旋的一侧主要是亲水的，另一侧主要是疏水的氨基酸残基。亲水侧的正电荷与带负电荷的原核细胞膜相互作用，疏水性侧与膜脂双层结合以使其渗透。由于昆虫外骨骼或表皮的表面高度疏水性，排斥水和污垢，因此可以预期两性化合物可以使其渗透。在酵母培养物中产生并表达了突变的 lycotoxin 1 肽，并将其喂食秋粘虫（Spodoptera frugiperda）幼虫，以鉴定最致命的突变体。蜘蛛毒液毒素（如 lycotoxin-1）在植物中的转基因表达可以提供持久的昆虫抗性。
