Background: Antimicrobial resistance is an emerging global health challenge that has led researchers to study alternatives to conventional antibiotics. A promising alternative is antimicrobial peptides (AMPs), produced as the first line of defense by almost all living organisms. To improve its biological activity, the conjugation of AMPs is a promising approach. Objective: In this study, we evaluated the N-terminal conjugation of p-Bt (a peptide derived from Bothrops Jararacuçu`s venom) with ferrocene (Fc) and gallic acid (GA). Acetylated and linear versions of p-Bt were also synthesized to evaluate the importance of N-terminal charge and dimeric structure. Methods: The compounds were obtained using solid-phase peptide synthesis. Circular dichroism, vesicle permeabilization, antimicrobial activity, and cytotoxicity studies were conducted. Results: No increase in antibacterial activity against Escherichia coli was observed by adding either Fc or GA to p-Bt. However, Fc-p-Bt and GA-p-Bt exhibited improved activity against Staphylococcus aureus. No cytotoxicity upon fibroblast was observed for GA-p-Bt. On the other hand, conjugation with Fc increased cytotoxicity. This toxicity may be related to the membrane permeabilization capacity of this bioconjugate, which showed the highest carboxyfluorescein leakage in vesicle permeabilization experiments. Conclusion: Considering these observations, our findings highlight the importance of adding bioactive organic compounds in the N-terminal position as a tool to modulate the activity of AMPs.

中文翻译：

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二茂铁和没食子酸缀合对 desCys11/Lys12/Lys13-(p-BthTX-I)2K 肽的影响：结构、通透性和抗菌活性

背景：抗生素耐药性是一个新兴的全球健康挑战，促使研究人员研究传统抗生素的替代品。一种有前途的替代品是抗菌肽（AMP），几乎所有生物体都会产生它作为第一道防线。为了提高其生物活性，AMP 的缀合是一种有前途的方法。目的：在本研究中，我们评估了 p-Bt（一种源自 Bothrops Jararacuçu 毒液的肽）与二茂铁 (Fc) 和没食子酸 (GA) 的 N 末端缀合。还合成了 p-Bt 的乙酰化和线性版本，以评估 N 端电荷和二聚体结构的重要性。方法：通过固相肽合成获得化合物。进行了圆二色性、囊泡通透性、抗菌活性和细胞毒性研究。结果：在 p-Bt 中添加 Fc 或 GA 后，未观察到对大肠杆菌的抗菌活性增加。然而，Fc-p-Bt 和 GA-p-Bt 对金黄色葡萄球菌的活性有所改善。未观察到 GA-p-Bt 对成纤维细胞的细胞毒性。另一方面，与 Fc 缀合增加了细胞毒性。这种毒性可能与该生物缀合物的膜通透能力有关，在囊泡通透实验中显示出最高的羧基荧光素渗漏。结论：考虑到这些观察结果，我们的研究结果强调了在 N 末端位置添加生物活性有机化合物作为调节 AMP 活性的工具的重要性。