Ketomethylene and (Cyanomethylene)amino Pseudopeptide Analogs of the C-Terminal Hexapeptide of Neurotensin

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Abstract
Supplementary Material Available: lH NMR data for compounds 1-10 and 13C NMR data for compound 15 (2 pages). Ordering information is given on any current masthead page.A series of pseudopeptide analogues of the C-terminal hexapeptide of neurotensin (NT8-13),\ud namely [Tyr11Y[COCH21Phe121-,[ Ile12Y[COCH21Phe131-a, nd [Tyr11Y[CH(CN)NHlIle121NT8-13\ud with different stereochemistries, has been synthesized and evaluated for its potency in\ud displacing labeled NT from rat cortex membranes. Ketomethylene pseudohexapeptides were\ud prepared from the corresponding Boc-protected ketomethylene dipeptide derivatives, previously\ud formed, using different solid phase synthesis (SPS) conditions, while (cyanomethy1ene)amino\ud analogues were directly prepared by SPS using Fmoc strategy. H-Arg-Arg-Pro-TyrY[COCH21-\ud Phe-Leu-OH was nearly as potent as NT8-13 and [Phel2lNT8-l3 in binding to the receptor.\ud Comparison of the affinities for the pseudohexapeptides, here reported, with those of the Y-\ud [CHzNH] analogues indicates the importance of the CO group in the amide or surrogate linkage\ud at 11-12 and 12-13 positions in the receptor binding process.Acknowledgment. We thank the Comisidn Interministerial\ud de Ciencia y Tecnologia (FAR 91-1 120-C02),\ud the Comunidad Authoma de Madrid (C167/91), and\ud Novo-Nordisk A/S for financial support. We are also\ud indebted to Mr. F. Caballero for the preparation of the\ud manuscript .Peer reviewe

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