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]³‐VmCT1‐NH₂, [Arg]⁷‐VmCT1‐NH₂, and [Arg]¹¹‐VmCT1‐NH₂, against Plasmodium gallinaceum sporozoites and MCF‐7 mammary cancer cells. Our screen identified peptides [Arg]³‐VmCT1‐NH₂ and [Arg]⁷‐VmCT1‐NH₂ as potent antiplasmodial agents (IC₅₀ of 0.57 and 0.51 μmol L⁻¹, respectively), whereas [Arg]¹¹‐VmCT1‐NH₂ 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.

中文翻译：

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净电荷调节调节源自蝎毒的肽的抗疟原虫和抗癌特性

VmCT1 是一种从蝎毒 Vaejovis mexicanus的毒液中分离出来的线性螺旋抗菌肽，对细菌、真菌和原生动物具有广谱抗菌活性。来自这种含有单一 Arg 替代物的肽的类似物已被证明可以增加对克氏锥虫的抗菌和抗寄生虫活性。在这里，我们测试了这些类似物对抗疟疾（一种由原生动物疟原虫引起的传染病）的作用，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] ³ -VmCT1-NH ₂、[Arg] ⁷ -VmCT1-NH ₂和 [Arg] ¹¹ -VmCT1-NH ₂, 对抗疟原虫子孢子和 MCF-7 乳腺癌细胞。我们的筛选鉴定肽 [Arg] ³ -VmCT1-NH ₂和 [Arg] ⁷ -VmCT1-NH ₂作为有效的抗疟原虫剂（IC _{50 分别}为 0.57 和 0.51 μmol L ^-1），而 [Arg] ¹¹ -VmCT1- NH ₂没有表现出对P. gallinaceum 的活性子孢子。有趣的是，所有肽都表现出针对 MCF-7 的活性，并对健康细胞表现出较低的细胞毒性。我们证明，通过精氨酸取代增加 VmCT1 的净正电荷，可调节该肽家族的生物学特性，产生新型抗疟原虫和抗肿瘤分子。