Importance of secondary structure for endothelin binding and functional activity.

ET-116-Phe] and ET-112-Pro] were prepared in order to investigate the importance of secondary structure of ET-1 for receptor binding and function. ET-116-Phe] displayed the greatest binding and contractile potency of the ET-analogs tested in rabbit pulmonary artery, rat aorta, and rat left atria. ET-112-Pro] also exhibited low nanomolar binding in these tissues but showed less contractile activity than ET-116-Phe] or ET-1. The results indicate that the helical region between residues Lys9 and Cys15 of ET-1 is not critical for receptor binding and functional activity. However, replacement of His16 with Phe altered the charge characteristics of the C-terminal region of ET-1 producing the most potent ET-1 analog yet reported.