1-deamino-1(15)-carba and -dicarba analogues of endothelin-1

Sulfanyl-methylene and ethylene bridges were inserted into the molecule of endothelin-1 (ET-1) as other possible isosteric replacements of its outer d isulfide linkage. The [1-deamino-1-carba]ET-1, [1-deamino-15-carba]ET-1 and [1-deamino-1,15-dicarba]ET-1 were synthesized either by a fragment condens ation of protected cyclic pentadecapeptides with carboxy-terminal hexapepti des of the endothelin-1 sequence or by step-wise coupling on polymer suppor t of the entire henicosapeptide sequences from carboxy-terminus. The analog ues were devoid of uterotonic activity in comparison with the parent ET-1.