A STRUCTURE-ACTIVITY STUDY OF A C-TERMINAL ENDOTHELIN ANALOG

We report a structure-activity study of an endothelin (ET) analogue, o btained by introduction of a non-aminoacidic portion on the C-terminal ET pentapeptide. The peptidic moiety was modified with systematic rep lacement of each residue by alanine (Ala scan); further modifications were performed at the C-terminus. The biological activity was analyzed at both ETA and ETU receptor subtypes, showing that the two C-termina l residues (Ile-Trp) are very important for the activity. On the contr ary, the aminoacidic central portion of the molecule appears to be muc h more tolerant toward modifications.