研究内皮素陷阱作为治疗内皮素-1相关疾病潜在治疗工具的特异性。
Investigating the specificity of endothelin-traps as a potential therapeutic tool for endothelin-1 related disorders.
作者信息
Jain Arjun, Bozovicar Kristof, Mehrotra Vidhi, Bratkovic Tomaz, Johnson Martin H, Jha Ira
机构信息
ET-Traps Limited, Cambridge CB3 0JE, United Kingdom.
Department of Pharmaceutical Biology, Faculty of Pharmacy, University of Ljubljana, Slovenia 1000, Slovenia.
出版信息
World J Diabetes. 2022 Jun 15;13(6):434-441. doi: 10.4239/wjd.v13.i6.434.
BACKGROUND
Endothelin (ET)-traps are Fc-fusion proteins with a design based on the physiological receptors of ET-1. Previous work has shown that use of the selected ET-traps potently and significantly reduces different markers of diabetes pathology back to normal, non-disease levels.
AIM
To demonstrate the selected ET-traps potently and significantly bind to ET-1.
METHODS
We performed phage display experiments to test different constructs of ET-traps, and conducted bio-layer interferometry binding assays to verify that the selected ET-traps bind specifically to ET-1 and display binding affinity in the double-digit picomolar range (an average of 73.8 rM, = 6).
RESULTS
These experiments have confirmed our choice of the final ET-traps and provided proof-of-concept for the potential use of constructs as effective biologics for diseases associated with pathologically elevated ET-1.
CONCLUSION
There is increased need for such therapeutics as they could help save millions of lives around the world.
背景
内皮素（ET）陷阱是基于ET-1生理受体设计的Fc融合蛋白。先前的研究表明，使用选定的ET陷阱可有效且显著地将糖尿病病理的不同标志物降低至正常、非疾病水平。
目的
证明选定的ET陷阱能有效且显著地与ET-1结合。
方法
我们进行了噬菌体展示实验以测试ET陷阱的不同构建体，并进行了生物层干涉术结合试验，以验证选定的ET陷阱能特异性结合ET-1，并在两位数皮摩尔范围内显示结合亲和力（平均73.8 rM，n = 6）。
结果
这些实验证实了我们对最终ET陷阱的选择，并为将构建体作为与病理升高的ET-1相关疾病的有效生物制剂的潜在用途提供了概念验证。
结论
对这类疗法的需求日益增加，因为它们有助于拯救全球数百万人的生命。
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