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芳香三肽的抗菌水凝胶。

Antibacterial hydrogels of aromatic tripeptides.

机构信息

Molecular Informatics and Design Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Assam, 781039, India.

Advanced Energy & Materials Systems Laboratory, Department of Chemical Engineering, Indian Institute of Technology Guwahati, Assam, 781039, India.

出版信息

Soft Matter. 2022 Aug 31;18(34):6360-6371. doi: 10.1039/d2sm00606e.

DOI:10.1039/d2sm00606e
PMID:35971808
Abstract

Self-assembled peptide hydrogels have emerged as alternatives to the conventional approaches employed in controlled drug release, wound-healing, and drug delivery, and as anti-infective agents. However, peptide hydrogels possessing antibacterial properties are less explored. In this work, we have designed three ultrashort antibacterial peptide hydrogels: Fmoc-FFH-CONH, Fmoc-FHF-CONH, and Fmoc-HFF-CONH. The rheological study showed the higher storage modulus of Fmoc-FFH-CONH (30.43 kPa) compared to Fmoc-FHF-CONH and Fmoc-HFF-CONH, which may be attributed to the enhanced aromatic interaction in Fmoc-FFH-CONH compared to the other two variants, resulting in more mechanical rigidity. Further, the prepared hydrogels were evaluated for their inherent antibacterial potency against Gram-positive (, strain MTCC 96) and Gram-negative (, strain PA01) bacteria. Antibacterial experiments demonstrated the potency of the hydrogels in the order of Fmoc-FFH-CONH > Fmoc-FHF-CONH > Fmoc-HFF-CONH. The antibacterial effect of the hydrogels was predominantly due to the osmotic stress and membrane disruption, which was verified by reactive oxygen species (ROS) generation and outer membrane permeabilization assays. Our findings point to the scope of using the synthesized peptide hydrogels as agents for topical applications.

摘要

自组装肽水凝胶已成为传统控制药物释放、伤口愈合和药物递送以及抗感染药物的替代方法。然而,具有抗菌性能的肽水凝胶的研究还较少。在这项工作中,我们设计了三种超短抗菌肽水凝胶:Fmoc-FFH-CONH、Fmoc-FHF-CONH 和 Fmoc-HFF-CONH。流变学研究表明,Fmoc-FFH-CONH 的储能模量(30.43 kPa)高于 Fmoc-FHF-CONH 和 Fmoc-HFF-CONH,这可能归因于与其他两种变体相比,Fmoc-FFH-CONH 中增强的芳族相互作用,导致更高的机械刚性。此外,还评估了所制备的水凝胶对革兰氏阳性(,MTCC 96 株)和革兰氏阴性(,PA01 株)细菌的固有抗菌效力。抗菌实验表明,水凝胶的效力顺序为 Fmoc-FFH-CONH>Fmoc-FHF-CONH>Fmoc-HFF-CONH。水凝胶的抗菌作用主要归因于渗透压和膜破坏,这通过活性氧(ROS)生成和外膜通透性测定得到验证。我们的研究结果表明,合成的肽水凝胶可作为局部应用的药物。

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