A novel GalR2-specific peptide agonist |
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| Authors: | Johan Runesson Indrek Saar Linda Lundström Jaak Järv Ülo Langel |
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| Affiliation: | 1. Department of Neurochemistry, Stockholm University, Svante Arrheniusv. 21A, SE-10691 Stockholm, Sweden;2. Institute of Technology, University of Tartu, Nooruse 1, 50411 Tartu, Estonia;3. F. Hoffman-La Roche AG, Pharmaceutical Division, CNS Research PRDNP, CH-4070 Basel, Switzerland;4. Institute of Chemistry, University of Tartu, 2 Jakobi Str, 51014 Tartu, Estonia |
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| Abstract: | The galanin peptide family and its three receptors have with compelling evidence been implicated in several high-order physiological disorders. The co-localization with other neuromodulators and the distinct up-regulation during and after pathological disturbances has drawn attention to this neuropeptide family. In the current study we present data on receptor binding and functional response for a novel galanin receptor type 2 (GalR2) selective chimeric peptide, M1145 (RG)2-N-galanin(2-13)-VL-(P)3-(AL)2-A-amide]. The M1145 peptide shows more than 90-fold higher affinity for GalR2 over GalR1 and a 76-fold higher affinity over GalR3. Furthermore, the peptide yields an agonistic effect in vitro, seen as an increase in inositol phosphate (IP) accumulation, both in the absence or the presence of galanin. The peptide design with a N-terminal extension of galanin(2-13), prevails new insights in the assembly of novel subtype specific ligands for the galanin receptor family and opens new possibilities to apply the galanin system as a putative drug target. |
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