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Self-Assembled Fmoc-Arg-Phe-Phe Peptide Gels with Highly Potent Bactericidal Activities
ACS Biomaterials Science & Engineering ( IF 5.4 ) Pub Date : 2020-09-07 , DOI: 10.1021/acsbiomaterials.0c00660 Neelam Chauhan 1 , Yashveer Singh 1
ACS Biomaterials Science & Engineering ( IF 5.4 ) Pub Date : 2020-09-07 , DOI: 10.1021/acsbiomaterials.0c00660 Neelam Chauhan 1 , Yashveer Singh 1
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The emergence of antibiotic resistance and the increasing rate of bacterial infections have motivated scientists to explore novel antibacterial materials and strategies to circumvent this challenge. Gels fabricated from ultrashort self-assembled peptides have turned out to be the most promising bactericidal materials. Self-assembled Fmoc-Phe-Phe gels have been extensively investigated earlier, and it has been shown that these gels possess potent bactericidal properties but suffer from disadvantages, such as poor proteolytic stabilities. In the present work, we report the highly potent bactericidal activities and proteolytic stability of gels fabricated from Fmoc-l-Arg-d-Phe-d-Phe-CONH2 (RFF) peptide, which are best in class. We fabricated and characterized self-assembled gels (1–2% w/v) from Fmoc-d-Phe-d-Phe-CONH2 (FF), Fmoc-l-His-d-Phe-d-Phe-CONH2 (HFF), and Fmoc-l-Arg-d-Phe-d-Phe-CONH2 (RFF) in aq dimethyl sulfoxide (35% v/v). The gels were characterized for their surface morphology, viscoelastic, self-healing, and stability characteristics. On incubation with proteolytic enzymes, FF gels did not show statistically significant degradation, and HFF and RFF gels showed only 43 and 32% degradation within 72 h at 37 °C, which is much better than gels reported earlier. The RFF gels (2%) exhibited more than 90% inhibition against Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive) within 6 h, and the activities were sustained for up to 72 h. The high-resolution transmission electron microscopy studies indicated electrostatic interactions between the gel and bacterial membrane components, leading to cell lysis and death, which was further confirmed by the bacterial cell Live/Dead assay. MTT assay showed that the gels were not toxic to mammalian cells (L929). The bactericidal characteristics of RFF gels have not been reported so far. The RFF gels show strong potential for treating device-related infections caused by antimicrobial-resistant bacteria.
中文翻译：
具有强力杀菌活性的自组装Fmoc-Arg-Phe-Phe肽凝胶
抗生素耐药性的出现和细菌感染率的上升，促使科学家们探索新型的抗菌材料和策略来规避这一挑战。由超短自组装肽制成的凝胶已被证明是最有前途的杀菌材料。自组装的Fmoc-Phe-Phe凝胶已被广泛研究，并且已经显示出这些凝胶具有强力的杀菌性能，但存在诸如蛋白水解稳定性差的缺点。在目前的工作中，我们报告了高度有效的杀菌活性和凝胶的蛋白水解稳定性从制造的Fmoc-升是-Arg- d -Phe- d -Phe-CONH 2（RFF）肽，这是同类产品中最好的。我们从Fmoc- d -Phe- d -Phe-CONH 2（FF），Fmoc - 1 -His- d -Phe- d -Phe-CONH 2制备并表征了自组装凝胶（1-2％w / v）。（HFF）和Fmoc- 1 -Arg- d -Phe- d -Phe-CONH 2（RFF）在二甲基亚砜水溶液（35％v / v）中。凝胶的特征在于其表面形态，粘弹性，自修复性和稳定性。与蛋白水解酶一起孵育时，FF凝胶未显示出统计学上的显着降解，HFF和RFF凝胶在37°C下72 h内仅显示了43％和32％的降解，这比之前报道的凝胶好得多。RFF凝胶（2％）对大肠杆菌（革兰氏阴性）和金黄色葡萄球菌的抑制作用超过90％（革兰氏阳性）在6小时内，并且活动持续长达72小时。高分辨率透射电子显微镜研究表明，凝胶和细菌膜成分之间存在静电相互作用，导致细胞裂解和死亡，细菌细胞活/死分析进一步证实了这一点。MTT分析表明该凝胶对哺乳动物细胞无毒（L929）。迄今为止，尚未报道RFF凝胶的杀菌特性。RFF凝胶显示出强大的潜力，可以治疗由抗药性细菌引起的设备相关感染。
更新日期：2020-10-12
中文翻译：
具有强力杀菌活性的自组装Fmoc-Arg-Phe-Phe肽凝胶
抗生素耐药性的出现和细菌感染率的上升，促使科学家们探索新型的抗菌材料和策略来规避这一挑战。由超短自组装肽制成的凝胶已被证明是最有前途的杀菌材料。自组装的Fmoc-Phe-Phe凝胶已被广泛研究，并且已经显示出这些凝胶具有强力的杀菌性能，但存在诸如蛋白水解稳定性差的缺点。在目前的工作中，我们报告了高度有效的杀菌活性和凝胶的蛋白水解稳定性从制造的Fmoc-升是-Arg- d -Phe- d -Phe-CONH 2（RFF）肽，这是同类产品中最好的。我们从Fmoc- d -Phe- d -Phe-CONH 2（FF），Fmoc - 1 -His- d -Phe- d -Phe-CONH 2制备并表征了自组装凝胶（1-2％w / v）。（HFF）和Fmoc- 1 -Arg- d -Phe- d -Phe-CONH 2（RFF）在二甲基亚砜水溶液（35％v / v）中。凝胶的特征在于其表面形态，粘弹性，自修复性和稳定性。与蛋白水解酶一起孵育时，FF凝胶未显示出统计学上的显着降解，HFF和RFF凝胶在37°C下72 h内仅显示了43％和32％的降解，这比之前报道的凝胶好得多。RFF凝胶（2％）对大肠杆菌（革兰氏阴性）和金黄色葡萄球菌的抑制作用超过90％（革兰氏阳性）在6小时内，并且活动持续长达72小时。高分辨率透射电子显微镜研究表明，凝胶和细菌膜成分之间存在静电相互作用，导致细胞裂解和死亡，细菌细胞活/死分析进一步证实了这一点。MTT分析表明该凝胶对哺乳动物细胞无毒（L929）。迄今为止，尚未报道RFF凝胶的杀菌特性。RFF凝胶显示出强大的潜力，可以治疗由抗药性细菌引起的设备相关感染。
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