This study evaluates the embryotoxicity of dithienylethene-modified peptides upon photoswitching, using 19 analogues based on the β-hairpin scaffold of the natural membranolytic peptide gramicidin S. We established an in vivo assay in two variations (with ex vivo and in situ photoisomerization), using larvae of the model organism Danio rerio, and determined the toxicities of the peptides in terms of 50% lethal doses (LD50). This study allowed us to: (i) demonstrate the feasibility of evaluating peptide toxicity with D. rerio larvae at 3-4 days post fertilization, (ii) determine the phototherapeutic safety windows for all peptides, (iii) demonstrate photoswitching of the whole-body toxicity for the dithienylethene-modified peptides in vivo, (iv) re-analyze previous structure-toxicity relationship data, and (v) select promising candidates for potential clinical development.

中文翻译：

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光可控的二噻吩基乙烯修饰的环状肽：光开关斑马鱼胚胎中的体内毒性。

这项研究使用基于天然膜分解肽短杆菌肽S的β-发夹结构的19种类似物，评估了二噻吩乙烯修饰的肽在光转换后的胚胎毒性。我们建立了两种体内变化的体外测定方法（离体和原位光异构化），使用模式生物Danio rerio的幼虫，并以50％致死剂量（LD50）来测定肽的毒性。这项研究使我们能够：（i）证明在受精后3-4天用雷氏假丝酵母幼虫评估肽毒性的可行性，（ii）确定所有肽的光疗安全窗口，（iii）证明整个-的光开关体内二噻吩乙烯改性肽的体内毒性，（iv）重新分析先前的结构-毒性关系数据，