Synthesis and structure-activity relationship studies of new endothelin pseudopeptide analogues containing alkyl spacers

We replaced the Asp(18)-Ile(19) dipeptide of the C-terminal ET analogue Ph- Ph-CH2-O-N=CH-CO-Phe-Asp-Ile-Ile-Trp- OH by alkyl spacers of various length s to investigate the role of the aminoacidic central portion of the molecul e and to define the N-terminal and C-terminal pharmacophoric regions of thi s analogue. The side-chains of the central dipeptide have been shown to be irrelevant for the binding of the molecule to the receptor, but the distanc e between the two postulated sites of interaction of the ligand with the ET B receptor appears to be fundamental. (C) 1999 Elsevier Science S.A. All ri ghts reserved.