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用于体内治疗真菌性角膜炎的短合成α-螺旋形成肽两亲物。

Short Synthetic α-Helical-Forming Peptide Amphiphiles for Fungal Keratitis Treatment In Vivo.

机构信息

Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, 138669, Singapore.

出版信息

Adv Healthc Mater. 2017 Mar;6(6). doi: 10.1002/adhm.201600777. Epub 2017 Jan 12.

DOI:10.1002/adhm.201600777
PMID:28081296
Abstract

The emergence of fungal keratitis is on the rise globally. However, current antifungal therapeutics are ineffective in severe keratomycosis. Previously reported α-helical peptides comprising 8-14 amino acids demonstrate broad-spectrum antimicrobial activity both in vitro and in vivo. Here, α-helical peptides of the optimized sequences are investigated for antifungal biofilm in vitro and in vivo using a fungal biofilm-caused mouse keratitis model. The peptides with the optimal composition demonstrate higher α-helical propensity and improve antifungal activity in dispersing Candida albicans biofilm in vitro. Moreover, the optimized α-helical peptides are not only effective in treating C. albicans biofilm-induced keratitis in mice, they are also nontoxic to the mice eyes. These peptides have the potential to be developed as antifungal agents for the treatment of C. albicans biofilm-caused keratitis.

摘要

真菌性角膜炎在全球范围内呈上升趋势。然而,目前的抗真菌疗法在严重的真菌性角膜感染中无效。先前报道的由 8-14 个氨基酸组成的α-螺旋肽在体外和体内均表现出广谱的抗菌活性。在这里,使用真菌性生物膜引起的小鼠角膜炎模型,研究了优化序列的α-螺旋肽在体外和体内的抗真菌生物膜活性。具有最佳组成的肽具有更高的α-螺旋倾向,并提高了体外分散白色念珠菌生物膜的抗真菌活性。此外,优化的α-螺旋肽不仅能有效治疗小鼠白色念珠菌生物膜诱导的角膜炎,而且对小鼠眼睛也没有毒性。这些肽有可能被开发为治疗白色念珠菌生物膜性角膜炎的抗真菌药物。

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