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
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.