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

Int J Pept Protein Res. 1993 Feb;41(2):181-4. doi: 10.1111/j.1399-3011.1993.tb00129.x.

Abstract

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.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Colon / drug effects
  • Guinea Pigs
  • In Vitro Techniques
  • Molecular Sequence Data
  • Muscle Relaxation / drug effects
  • Neurotensin / analogs & derivatives*
  • Neurotensin / chemical synthesis
  • Neurotensin / pharmacology
  • Oligopeptides / chemical synthesis
  • Oligopeptides / chemistry
  • Oligopeptides / pharmacology
  • Oxidation-Reduction
  • Peptide Fragments / chemical synthesis
  • Peptide Fragments / chemistry
  • Peptide Fragments / pharmacology
  • Prosencephalon / metabolism
  • Rats
  • Structure-Activity Relationship

Substances

  • Oligopeptides
  • Peptide Fragments
  • Neurotensin