Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 16/10 Miklukho-Maklaya str., Moscow, 117997 Russia.
Biological Faculty, Lomonosov Moscow State University, 119234 Moscow, Russia.
Future Med Chem. 2018 Oct 1;10(19):2309-2322. doi: 10.4155/fmc-2018-0170. Epub 2018 Sep 14.
Spider venom is a rich source of antibacterial peptides, whose hemolytic activity is often excessive.
How to get rid of it? Using latarcins from Lachesana tarabaevi and oxyopinin Oxt 4a from Oxyopes takobius spider venoms we performed coarse-grained molecular dynamics simulations of these peptides in the presence of lipid bilayers, mimicking erythrocyte membranes. This identified hemolytically active fragments within Oxt 4a and latarcins. Then, we synthesized five 20-residue peptides, containing different parts of the Oxt 4a and latarcin-1 sequence, carrying mutations within the identified regions.
The antibacterial and hemolytic tests suggested that the three of the synthesized peptides demonstrated substantial decrease in hemolytic activity, retaining, or even exceeding antibacterial potential of the parent peptides.
蜘蛛毒液是抗菌肽的丰富来源，但其溶血活性往往过高。
如何去除它？利用拉沙纳塔拉拉比蛛（Lachesana tarabaevi）中的拉卡丁（latarcin）和奥克托皮宁 Oxt 4a 以及奥克皮斯塔科比乌蛛（Oxyopes takobius）毒液中的这两种肽进行粗粒度分子动力学模拟，模拟红细胞膜存在于脂质双层中。这确定了 Oxt 4a 和拉卡丁内具有溶血活性的片段。然后，我们合成了五个包含 20 个残基的肽，其中包含 Oxt 4a 和拉卡丁-1 序列的不同部分，在鉴定区域内携带突变。
抗菌和溶血试验表明，合成的三种肽的溶血活性显著降低，同时保留甚至增强了亲本肽的抗菌潜力。
