Important pharmacophores for binding to galanin receptor 2

Galanin(2-11) has been introduced as a receptor subtype selective ligand for the GalR2 subtype of the galanin receptors, and has gained use in pharmacological studies of galaninergic signaling in the past two years. By introducing L-Ala substitutions in the galanin(2-11) sequence, we have examined the amino acid residues which are of importance for binding to the GalR2 receptor. Our study shows that Trp(2), Asn(5), Gly(8) and Tyr(9) are of great importance for high affinity binding. When placed in an alpha-helical conformation, the side chains of these residues are, with the exception of Tyr(9), displayed on the same side of the peptide. This information is useful in the rational design of non-peptide type GalR2 receptor ligands. (c) 2005 Elsevier Ltd. All rights reserved.