Binding of Chimeric Peptides M617 and M871 to Galanin Receptor Type 3 Reveals Characteristics of Galanin Receptor-Ligand Interaction

作者：Sollenberg Ulla E; Runesson Johan; Sillard Rannar; Langel Ulo^*

来源：International Journal of Peptide Research and Therapeutics, 2010, 16(1): 17-22.

DOI：10.1007/s10989-009-9197-9

• GPCR
• Galanin
• Galanin receptor type 3
• GalR3
• Chimeric peptide

The neuropeptide galanin is ascribed to a variety of biological effects, but selective compounds to examine the specific roles of the three receptor subtypes are currently lacking. The recently introduced chimeric peptide ligands M617 and M871 target the galanin receptors GalR1 and GalR2, respectively. These peptides have been used to examine receptor function in vitro and in vivo, but their affinity to GalR3 has not been tested. Here, we report the binding affinity of these peptides at human GalR3 and demonstrate that M617 binds GalR3 and stimulates this receptor in an agonistic manner, whereas M871 shows very low affinity towards GalR3 (K (i) 49.2 +/- A 9.4 nM and > 10 mu M, respectively). An l-alanine scan of M617 revealed the importance of the ligand C-terminus in GalR3 binding, which stands in contrast to the structural requirements for binding to GalR1 and GalR2. These data provide insights into galanin receptor ligand binding that should be considered when using these compounds in functional studies.

• 出版日期2010-3