Structural study of the N-terminal segment of neuropeptide tyrosine.
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.
Forest
M
M
Institut National de la Recherche, Scientifique-Santé (INRS-Santé), Université du Québec, Pointe-Claire, Canada.
Martel
J C
JC
St-Pierre
S
S
Quirion
R
R
Fournier
A
A
D000409:Alanine; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009478:Neuropeptide Y / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D014649:Vas Deferens / Q000187:drug effects / Q000378:metabolism
D009478:Neuropeptide Y; D010446:Peptide Fragments; D000409:Alanine