Investigating the specificity of endothelin-traps as a potential therapeutic tool for endothelin-1 related disorders

World J Diabetes. 2022 Jun 15;13(6):434-441. doi: 10.4239/wjd.v13.i6.434.

Abstract

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, n = 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.

Keywords: Chronic kidney disease; Diabetes; Endothelin-1; Endothelin-traps; Heart failure; Novel therapeutic.