KETOMETHYLENE AND (CYANOMETHYLENE)AMINO PSEUDOPEPTIDE ANALOGS OF THE C-TERMINAL HEXAPEPTIDE OF NEUROTENSIN

A series of pseudopeptide analogues of the C-terminal hexapeptide of neurotensin (NT8-13), namely [Tyr(11)Psi[COCH2]Phe(12)]-, [Ile(12)Psi[COCH2]Phe(13)]-, and [Tyr(11)Psi[CH(CN)NH]Ile(12)]NT8-13 with different stereochemistries, has been synthesized and evaluated for its potency in displacing labeled NT from rat cortex membranes. Ketomethylene pseudohexapeptides were prepared from the corresponding Boc-protected ketomethylene dipeptide derivatives, previously formed, using different solid phase synthesis (SPS) conditions, while (cyanomethylene)amino analogues were directly prepared by SPS using Fmoc strategy. H-Arg-Arg-Pro-Tyr Psi[COCH2]-Phe-Leu-OH was nearly as potent as NT8-13 and [Phe(12)]NT8-13 in binding to the receptor. Comparison of the affinities for the pseudohexapeptides, here reported, with those of the Psi-[CH2NH] analogues indicates the importance of the CO group in the amide or surrogate linkage at 11-12 and 12-13 positions in the receptor binding process.