Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, SP, 09210580, Brazil.
Departamento de Biofísica, Universidade Federal de São Paulo, São Paulo, SP, 04044020, Brazil.
J Pept Sci. 2021 Apr;27(4):e3296. doi: 10.1002/psc.3296. Epub 2021 Jan 13.
VmCT1, a linear helical antimicrobial peptide isolated from the venom of the scorpion Vaejovis mexicanus, displays broad spectrum antimicrobial activity against bacteria, fungi, and protozoa. Analogs derived from this peptide containing single Arg-substitutions have been shown to increase antimicrobial and antiparasitic activities against Trypanossoma cruzi. Here, we tested these analogs against malaria, an infectious disease caused by Plasmodium protozoa, and assessed their antitumoral properties. Specifically, we tested VmCT1 synthetic variants [Arg] -VmCT1-NH , [Arg] -VmCT1-NH , and [Arg] -VmCT1-NH , against Plasmodium gallinaceum sporozoites and MCF-7 mammary cancer cells. Our screen identified peptides [Arg] -VmCT1-NH and [Arg] -VmCT1-NH as potent antiplasmodial agents (IC of 0.57 and 0.51 μmol L , respectively), whereas [Arg] -VmCT1-NH did not show activity against P. gallinaceum sporozoites. Interestingly, all peptides presented activity against MCF-7 and displayed lower cytotoxicity toward healthy cells. We demonstrate that increasing the net positive charge of VmCT1, through arginine substitutions, modulates the biological properties of this peptide family yielding novel antiplasmodial and antitumoral molecules.
从蝎毒液中分离得到的线性螺旋抗菌肽 VmCT1 对细菌、真菌和原生动物具有广谱抗菌活性。该肽的衍生类似物含有单个 Arg 取代，已被证明能提高抗 Trypanossoma cruzi 的抗菌和抗寄生虫活性。在这里，我们测试了这些类似物对疟疾的作用，疟疾是一种由疟原虫引起的传染病，并评估了它们的抗肿瘤特性。具体来说，我们测试了 VmCT1 合成变体 [Arg] -VmCT1-NH 、[Arg] -VmCT1-NH 和 [Arg] -VmCT1-NH 对禽疟原虫孢子和 MCF-7 乳腺癌细胞的作用。我们的筛选结果表明，肽 [Arg] -VmCT1-NH 和 [Arg] -VmCT1-NH 是有效的抗疟原虫剂（IC 分别为 0.57 和 0.51 μmol L ），而 [Arg] -VmCT1-NH 对禽疟原虫孢子没有活性。有趣的是，所有的肽都对 MCF-7 表现出活性，并且对健康细胞的细胞毒性较低。我们证明，通过 Arg 取代增加 VmCT1 的净正电荷，可以调节该肽家族的生物学特性，从而产生新的抗疟原虫和抗肿瘤分子。
