SYNTHESIS OF SUBSTANCE-P C-TERMINAL HEXAPEPTIDE ANALOGS AND THEIR BIOLOGICAL-ACTIVITY - ANALOGS WITH ANTAGONISTIC ACTIVITY WITHOUT CONTAINING D-AMINO ACIDS

Analogues of the C-terminal hexapeptide of substance P have been synth esized in which each amino-acid residue was replaced by the bulky and strong lipophilic residue Asp(OBz1). The amino-acid residue of other s elected places has also been replaced by Glu(OBz1) or Glu(OCH3). The r esulting analogues were assayed for agonistic and antagonistic activit y in 3 biological preparations, GPI, RC and RPV, which have been propo sed as representative of the NK-1, NK-2 and NK-3 receptors, respective ly. Although none of the analogues contained D-amino acids, they showe d antagonistic activity according to the receptor type. Structure-acti vity relationships are also reported.