Synthesis of substance-P C-terminal hexapeptide analogues and their biological activity. Analogues with antagonistic activity without containing D-amino acids

Abstract Analogues of the C-terminal hexapeptide of substance P have been synthesized in which each amino-acid residue was replaced by the bulky and strong lipophilic residue Asp(OBzl). The amino-acid residue of other selected places has also been replaced by Glu(OBzl) or Glu(OCH 3 ). The resulting analogues were assayed for agonistic and antagonistic activity in 3 biological preparations, GPI, RC and RPV, which have been proposed as representative of the NK-1, NK-2 and NK-3 receptors, respectively. Although none of the analogues contained d -amino acids, they showed antagonistic activity according to the receptor type. Structure-activity relationships are also reported.