A galanin(2-11) analogue specific for GalR2

The neuropeptide galanin family currently consists of four members, namely galanin, galanin-message-associated peptide (GMAP), galanin-like peptide (GALP) and alarin. Galanin has been shown to influence several physiological processes including cognition, affective behavior, nerve injury, Alzheimer’s disease, neuroregeneration, seizures, feeding, and hormone release. The co-localization with other neuromodulators and the distinct up-regulation during and after pathological disturbances has drawn attention to this neuropeptide family. The regionally specific expression of the galanin receptors (GalR1-3) suggests different physiological roles, a feature which mostly remains unexplored due to the lack of stable, selective and potent ligands acting on the galanin receptor subtypes. The introduction of galanin(2-11) as a GalR2 selective ligand was an important advance in the galanin field. Unfortunately, later publications described that galanin(2-11) also binds with similar affinity to GalR3, a critical limitation when delineating the interplay between galanin receptor subtypes. Even so, galanin(2-11) has been given extensive attention and been used in numerous study as a non-GalR1 ligand. We now introduce an analogue of galanin(2-11) that combines the GalR2 selective binding, comparable with the published M1145 with the small size of galanin(2-11). Utilizing this true GalR2 selective ligand will help to define the role GalR2 in general and especially for already published studies that has been exploit galanin(2-11).