DEVELOPMENT OF ETB SELECTIVE AGONISTS - SOLUTION STRUCTURE OF A LINEAR ENDOTHELIN-1 ANALOG, ET-1 [CYS(ACM)(1,15), ALA(3), LEU(7), DASP(8), AIB(11)]

The solution structure of a synthetic ETB selective agonist, ET-1[Cys( Acm)(1,15), Ala(3), Leu(7), dAsp(8), Aib(11)] has been solved by H-1 N MR and molecular modelling studies. Such solution structures of linear modified peptides in aqueous methanol are being used in an ongoing pr ogram of research designed to assist in an understanding of the basic structural requirements for the biological activity of vasoconstrictor s. The resulting structure of this peptide is characterised by an alph a-helical conformation between residues Leu(6)-His(16) and by N- and C -termini which assume no defined conformation. A knowledge of the solu tion structures of this and related peptides, which are ETB selective agonists, are proving to be important in the understanding of how they interact with the ETB receptor.