A series of peptides with a long fatty acyl chain covalently attached to the C-terminal part and a free amine (-NH₂) group at the N-terminus have been designed so that these molecules can be assembled in aqueous medium by using various noncovalent interactions. Five different peptide amphiphiles with a general chemical formula [H₂N-(CH₂)_nCONH-Phe-CONHC₁₂ (n = 1–5, C₁₂ = dodecylamine)] have been synthesized, characterized, and examined for self-assembly and hydrogelation. All of these molecules [P1 (n = 1), P2 (n = 2), P3 (n = 3), P4 (n = 4), P5 (n = 5)] form thermoresponsive hydrogels in water (pH 6.6) with a nanofibrillar network structure. Interestingly, the hydrogels obtained from compounds P4 and P5 exhibit potential antimicrobial activity against Gram-positive bacteria (Staphylococcus aureus, Bacillus subtilis) and Gram-negative bacteria (Escherichia coli). Dose-dependent cell-viability studies using MTT assay (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) by taking human lung carcinoma (A549) cells vividly demonstrates the noncytotoxic nature of these gelator molecules in vitro. Hemolytic studies show nonsignificant or little hemolysis of human erythrocyte cells at the minimum inhibitory concentration (MIC) of these tested bacteria. Interestingly, it has been found that these antibacterial noncytotoxic hydrogels exhibit proteolytic resistance toward the enzymes proteinase K and chymotrypsin. Moreover, the gel strength and gel recovery time have been successfully modulated by varying the alkyl chain length of the N-terminally located amino acid residues. Similarly, the thermal stability of these hydrogels has been nicely tuned by altering the alkyl chain length of the N-terminally located amino acid residues. In the era of antibiotic-resistant strains of bacteria, the discovery of this new class of peptide-based antibacterial, proteolytically stable, injectable, and noncytotoxic soft materials holds future promise for the development of new antibiotics.

中文翻译：

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基于两亲性肽的超分子，无细胞毒性，具有刺激活性的水凝胶

设计了一系列肽链，这些肽链的长链上带有共价键的长脂肪酰基链，在N端带有一个游离胺基（-NH ₂），因此这些分子可以通过使用各种非共价键在水性介质中组装互动。已合成，表征和检查了五种不同的通式为[H ₂ N-（CH ₂）_n CONH-Phe-CONHC ₁₂（n = 1-5，C ₁₂ =十二烷基胺）的肽两亲物。和水凝胶化。所有这些分子[ P1（n = 1），P2（n = 2），P3（n = 3），P4（n = 4），P5（n = 5）]在具有纳米原纤网络结构的水中（pH 6.6）形成热响应性水凝胶。有趣的是，从化合物P4和P5获得的水凝胶对革兰氏阳性菌（金黄色葡萄球菌，枯草芽孢杆菌）和革兰氏阴性菌（大肠杆菌）具有潜在的抗菌活性。）。使用MTT分析法（3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四唑溴化物）进行剂量依赖性细胞生存力研究，通过摄取人肺癌（A549）细胞生动地证明了这些胶凝剂分子的非细胞毒性性质体外。溶血研究显示，在这些被测细菌的最低抑制浓度（MIC）下，人类红细胞的溶血作用不明显或几乎没有。有趣的是，已经发现这些抗菌的非细胞毒性水凝胶对蛋白酶K和胰凝乳蛋白酶表现出蛋白水解抗性。此外，已经通过改变位于N末端的氨基酸残基的烷基链长度成功地调节了凝胶强度和凝胶恢复时间。相似地，这些水凝胶的热稳定性已经通过改变位于N末端的氨基酸残基的烷基链长度进行了很好的调节。在对细菌具有抗生素抗性的菌株时代，这种新型的基于肽的抗菌，蛋白水解稳定，可注射且无细胞毒性的软材料的发现为新型抗生素的开发提供了未来的希望。