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源自蜘蛛毒素latarcin-3a的第一代多功能肽。

First generation of multifunctional peptides derived from latarcin-3a from spider toxin.

作者信息

de Moraes Luiz Filipe Ramalho Nunes, Silva Patrícia Souza E, Pereira Tábata Camila Pereira Leite, Almeida Rodrigues Thiago Antônio, Farias Frihling Breno Emanuel, da Costa Rosiane Andrade, Torquato Heron Fernandes Vieira, Lima Cauê Santos, Paredes-Gamero Edgar Julian, Migliolo Ludovico

机构信息

S-Inova Biotech, Programa de Pós-Graduação em Biotecnologia, Universidade Católica Dom Bosco, Campo Grande, MS, Brazil.

Selkis Biotech, Startup, Laboratório de Artrópodes Peçonhentos, Campo Grande, MS, Brazil.

出版信息

Front Microbiol. 2022 Sep 21;13:965621. doi: 10.3389/fmicb.2022.965621. eCollection 2022.

Abstract

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 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. Anti-biofilm tests were then performed to obtain MICs, where the peptides demonstrated activity from 4 to 128 μg.ml. 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. 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.

摘要

鉴于全球因细菌感染或肿瘤细胞导致的死亡人数,发现能够选择性作用于病原体的新化合物的需求日益明显。人们正在寻找新的多功能生物技术工具,包括蜘蛛毒液中存在的具有高生物技术潜力的化合物。本研究旨在对源自蜘蛛毒素latarcin-3a的合成肽进行合理设计和功能评估。测试了其对革兰氏阳性和阴性细菌的抗菌活性,最低抑菌浓度(MIC)在4至128μg/ml之间。随后进行了抗生物膜测试以获得MIC,这些肽在4至128μg/ml时表现出活性。对肿瘤细胞系C1498、Kasumi-1、K-562、Jurkat、MOLT4和Raji进行了细胞毒性测定。在合成肽类似物存在的情况下评估红细胞完整性,该类似物在128μg/ml时未促进溶血。表现出最佳抗菌活性的肽是Lt-MAP3,最佳抗肿瘤肽是Lt-MAP2。总之,多功能抗菌肽的合理设计可能是治疗细菌感染和肿瘤细胞等新兴疾病的有前景的替代工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2fc/9532841/1b64f977ee5f/fmicb-13-965621-g001.jpg

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