Data_Sheet_1_First generation of multifunctional peptides derived from latarcin-3a from Lachesana tarabaevi spider toxin.DOCX

The need for discovering new compounds that can act selectively on pathogens is becoming increasingly evident, given the number of deaths worldwide due to bacterial infections or tumor cells. New multifunctional biotechnological tools are being sought, including compounds present in spider venoms, which have high biotechnological potential. The present work aims to perform the rational design and functional evaluation of synthetic peptides derived from Lachesana tarabaevi spider toxin, known as latarcin-3a. The antimicrobial activity was tested against Gram-positive and -negative bacteria, with minimum inhibitory concentrations (MIC) between 4 and 128 μg.ml−1. Anti-biofilm tests were then performed to obtain MICs, where the peptides demonstrated activity from 4 to 128 μg.ml−1. In vitro cell cytotoxicity assays were carried out from tumor cell lines, lineages C1498, Kasumi-1, K-562, Jurkat, MOLT4, and Raji. Erythrocyte integrity was evaluated in the presence of synthetic peptides analog, which did not promote hemolysis at 128 μg.ml−1. The peptide that showed the best antibacterial activity was Lt-MAP3 and the best antitumor was Lt-MAP2. In conclusion, rational design of multifunctional antimicrobial peptides may be promising alternative tools in the treatment of emerging diseases such as bacterial infections and tumor cells.

鉴于全球因细菌感染或肿瘤细胞引发的死亡病例不断增多，开发可选择性作用于病原体的新型化合物的需求愈发迫切。目前科研人员正积极探寻新型多功能生物技术工具，其中蜘蛛毒液中含有的化合物便具备极高的生物技术开发潜力。本研究旨在对源自塔拉拉巴文蜘蛛（Lachesana tarabaevi）毒素的合成肽（即已知的latarcin-3a）开展合理设计与功能评价。研究针对革兰氏阳性菌与革兰氏阴性菌测试了其抗菌活性，其最小抑菌浓度（Minimum Inhibitory Concentrations, MIC）介于4至128 μg·ml⁻¹之间。随后开展了抗生物膜测试以获取其MIC值，结果显示该类合成肽的活性浓度范围同样为4至128 μg·ml⁻¹。针对肿瘤细胞系（包括C1498、Kasumi-1、K-562、Jurkat、MOLT4及Raji细胞系）开展了体外细胞毒性实验。同时评估了合成肽类似物存在时的红细胞完整性，结果显示其在128 μg·ml⁻¹浓度下未引发溶血反应。其中抗菌活性最优的合成肽为Lt-MAP3，抗肿瘤活性最优的为Lt-MAP2。综上，多功能抗菌肽的合理设计有望成为治疗细菌感染、肿瘤细胞相关疾病等新兴病症的极具前景的替代手段。