Structural study of the N-terminal segment of neuropeptide tyrosine

J Med Chem. 1990 Jun;33(6):1615-9. doi: 10.1021/jm00168a014.


A series of analogues of neuropeptide tyrosine (NPY) was synthesized by solid-phase peptide synthesis using BOP as a coupling reagent for the complete synthesis. A structure-activity study of the N-terminal portion of the molecule was performed with the analogues obtained by the successive replacement of the first 10 amino acids by the residue L-alanine. NPY and its analogues [Ala1-10]hNPY were tested for their potency on rat vas deferens and for their affinity to central nervous system receptors on a rat brain membrane preparation. The results suggest that the hypothetical polyproline type II helix structure of the N-terminal segment is involved in both potency and affinity. Indeed, the substitution by L-Ala of proline residues in position 2, 5, or 8 showed important losses of activity and affinity. The more important losses were observed with the replacement of Pro-5 or Pro-8. A critical loss of potency of hNPY was also observed after the substitution of the Tyr-1 residue by L-Ala, thus confirming the important role played by this residue for the full expression of the biological activity of NPY.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine*
  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • In Vitro Techniques
  • Male
  • Neuropeptide Y / analogs & derivatives*
  • Neuropeptide Y / chemical synthesis
  • Neuropeptide Y / metabolism
  • Peptide Fragments / chemical synthesis
  • Peptide Fragments / metabolism
  • Peptide Fragments / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Structure-Activity Relationship
  • Vas Deferens / drug effects
  • Vas Deferens / metabolism


  • Neuropeptide Y
  • Peptide Fragments
  • Alanine