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 ...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.展开更多
文摘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.
