Solid-phase synthesis of [Ala1,3,11,15]-endothelin-1 by a modified double-coupling procedure.

[Ala1,3,11,15]-Endothelin-1, a linear analogue of endothelin-1 in which alanines replace the cystine residues, has been prepared by solid-phase synthesis in approximately 17% yield. Fmoc amino acids were coupled using an economical modified double-coupling (symmetrical anhydride followed by O-benzotriazolyl ester) procedure under fully automated conditions. Conditions for synthesis and purification were closely monitored and should be applicable to other endothelin analogues.