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.
Couder
J
J
Eenheid Organische Chemie, Vrije Universiteit Brussel, Belgium.
Tourwé
D
D
Van Binst
G
G
Schuurkens
J
J
Leysen
J E
JE
D000595:Amino Acid Sequence; D000818:Animals; D003106:Colon / Q000187:drug effects; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009126:Muscle Relaxation / Q000187:drug effects; D009496:Neurotensin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D010084:Oxidation-Reduction; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D016548:Prosencephalon / Q000378:metabolism; D051381:Rats; D013329:Structure-Activity Relationship
D009842:Oligopeptides; D010446:Peptide Fragments; D009496:Neurotensin