Synthesis and biological activities of psi (CH2NH) pseudopeptide analogues of the C-terminal hexapeptide of neurotensin.

Each peptide CO-NH function in the biologically important C-terminal 8-13 sequence of neurotensin was replaced by the reduced CH2-NH isostere using the rapid in situ solid phase procedure developed by Sasaki & Coy. In general this modification resulted in a drop in receptor affinity except for the [Arg psi(CH2NH) Arg]-NT8-13 analogue (PIC50 9.23 vs. NT8-13 pIC50 8.03). This analogue also showed enhanced enzymatic stability, but acted as a full agonist as shown by the observation of relaxations of guinea-pig colon ascendens.