School of Biological Sciences, Indian Association for the Cultivation of Science, 2A & 2B Raja S. C. Mullick Road, Jadavpur, Kolkata-700032, India.
Laboratory of Catalysis and Chemical Biology, Department of Organic and Medicinal Chemistry, CSIR-Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Kolkata-700 032, India.
Soft Matter. 2022 Sep 28;18(37):7201-7216. doi: 10.1039/d2sm00562j.
Nanoscale self-assembly of peptide constructs represents a promising means to present bioactive motifs to develop new functional materials. Here, we present a series of peptide amphiphiles which form hydrogels based on β-sheet nanofibril networks, several of which have very promising anti-microbial and anti-parasitic activities, in particular against multiple strains of including drug-resistant ones. Aromatic amino acid based amphiphilic supramolecular gelators C-Phe-CONH-(CH)-NH ( = 6 for P1 and = 2 for P3) and C-Trp-CONH-(CH)-NH ( = 6 for P2 and = 2 for P4) have been synthesized and characterized, and their self-assembly and gelation behaviour have been investigated in the presence of ultrapure water (P1, P2, and P4) or 2% DMSO(v/v) in ultrapure water (P3). The rheological, morphological and structural properties of the gels have been comprehensively examined. The amphiphilic gelators (P1 and P3) were found to be active against both Gram-positive bacteria and Gram-negative bacteria and . Interestingly, amphiphiles P1 and P3 containing an L-phenylalanine residue show both antibacterial and antiparasitic activities. Herein, we report that synthetic amphiphiles with an amino acid residue exhibit a potent anti-protozoan activity and are cytotoxic towards a wide array of protozoal parasites, which includes Indian varieties of and also kill resistant parasitic strains including BHU-575, MIL and CPT cells. These gelators are highly cytotoxic to promastigotes of and trigger apoptotic-like events inside the parasite. The mechanism of killing the parasite is shown and these gelators are non-cytotoxic to host macrophage cells indicating the potential use of these gels as therapeutic agents against multiple forms of leishmaniasis in the near future.
纳米级自组装肽结构代表了一种很有前途的方法，可以将生物活性基序呈现出来，以开发新的功能材料。在这里，我们提出了一系列的肽两亲物，它们基于β-折叠纳米纤维网络形成水凝胶，其中一些具有非常有前途的抗微生物和抗寄生虫活性，特别是对多种包括耐药菌株。合成并表征了基于芳香族氨基酸的两亲超分子凝胶剂 C-Phe-CONH-(CH)-NH（ = 6 用于 P1 和 = 2 用于 P3）和 C-Trp-CONH-(CH)-NH（ = 6 用于 P2 和 = 2 用于 P4），并研究了它们在超纯水（P1、P2 和 P4）或 2% DMSO(v/v)在超纯水中（P3）存在下的自组装和凝胶行为。全面研究了凝胶的流变学、形态和结构特性。发现两亲性凝胶剂（P1 和 P3）对革兰氏阳性菌和革兰氏阴性菌都有活性。有趣的是，含有 L-苯丙氨酸残基的两亲体 P1 和 P3 表现出抗菌和抗寄生虫活性。在此，我们报告含有氨基酸残基的合成两亲物具有很强的抗原生动物活性，对多种原生动物寄生虫具有细胞毒性，包括印度品种的 和也能杀死耐药寄生虫株，包括 BHU-575、MIL 和 CPT 细胞。这些凝胶剂对前鞭毛体高度细胞毒性，并在寄生虫内部引发类似凋亡的事件。显示了杀死寄生虫的机制，这些凝胶剂对宿主巨噬细胞无细胞毒性，表明这些凝胶在不久的将来有可能作为治疗多种形式利什曼病的药物。
