NOVEL GALANIN RECEPTOR LIGANDS

Galanin is a neuroendocrine peptide which is 29/30 amino acids in leng th and is recognised by G-protein-coupled central nervous system recep tors via its N-terminus. We synthesised several galanin receptor ligan ds and fragments around C-terminal extensions of galanin(1-13) to yiel d chimeric peptides with C-terminals corresponding to bioactive peptid es like bradykinin(2-9), mastoparan, neuropeptide Y(25-36) or substanc e P(5-11), respectively. We also synthesised short galanin analogs in which galanin(1-13) was C-terminally elongated with Lys(14); different pharmacologically active small molecules were then attached to the E- amino group of Lys(14) Several cysteine-substituted linear and ring cl osed analogs of galanin(1-9) and galanin(1-16) were also synthesised. The equilibrium binding constants for these peptides at hypothalamic g alanin receptors were determined and found in the subnanomolar to micr omolar range. The large number of peptides and their binding affinitie s presented here permit structure-activity relationship analysis of pe ptide-type ligands to galanin receptors. (C) Munksgaard 1997.