SYNTHESIS AND STRUCTURE-ACTIVITY RELATIONSHIP OF SCYLIORHININ I ANALOGS MODIFIED IN POSITIONS 3,6,7 AND 8

Seven analogues of scyliorhinin I modified in positions 3, 6. 7 and 8 were synthesized by the solid-phase method. Their agonistic activity w as determined on isolated guinea pig ileum (GPI). Except for two analo gues modified in position 6. all exhibited dose-dependent activity. An alogues with Phe, D-Phe(F) in position 7 and Abu in position 8 appeare d significantly more active than scyliorhinin I and substance P, where as the analogue with NMeLeu in position 8 appeared to be twice as acti ve as the native molecule, but displayed only 12% or the substance P a ctivity. CD studies indicated that the analogues modified in position 8 behaved differently in the surroundings that mimics the biological m embranes.