STRUCTURE-AFFINITY STUDIES OF C-TERMINALLY MODIFIED ANALOGS OF NEUROPEPTIDE-Y LED TO A NOVEL CLASS OF PEPTIDIC Y-1 RECEPTOR ANTAGONIST

Citation
S. Hoffmann et al., STRUCTURE-AFFINITY STUDIES OF C-TERMINALLY MODIFIED ANALOGS OF NEUROPEPTIDE-Y LED TO A NOVEL CLASS OF PEPTIDIC Y-1 RECEPTOR ANTAGONIST, Regulatory peptides, 65(1), 1996, pp. 61-70
Citations number
35
Categorie Soggetti
Endocrynology & Metabolism",Physiology
Journal title
ISSN journal
01670115
Volume
65
Issue
1
Year of publication
1996
Pages
61 - 70
Database
ISI
SICI code
0167-0115(1996)65:1<61:SSOCMA>2.0.ZU;2-2
Abstract
A novel type of C-terminally modified analogs of the 36-mer peptide ho rmone neuropeptide Y has been synthesized, characterized and tested wi th respect to receptor affinity and biological activity in various sys tems, The compounds were obtained by synthesizing the fully protected peptide fragment NPY 1-35 or analogs of this, and coupling it in solut ion to various amines, alcohols, and modified tyrosine residues, It co uld be confirmed, that the C-terminal tyrosineamide of NPY is essentia l for its affinity to the Y-1 receptor subtype. Obviously, the amino g roup of the amide part is more important than the oxygene atom of the carbonyl group, as NPY 1-35-tyrosinol has a lower affinity than NPY 1- 35-tyrosinethioamide. NPY 1-35-tyramide could be shown to act as an an tagonist in a Ca2+ release assay in human neuroblastoma cells. Analogs of NPY 1-35-tyramide showed the same structure-affinity relationships as NPY itself, suggesting, that there exists the same binding mode fo r the agonist and the antagonist.