10.07.2015 Views

Proceedings book download - 5Z.com

Proceedings book download - 5Z.com

Proceedings book download - 5Z.com

SHOW MORE
SHOW LESS

You also want an ePaper? Increase the reach of your titles

YUMPU automatically turns print PDFs into web optimized ePapers that Google loves.

Results and DiscussionThe M1154 was designed to eliminate a biological response from the GalR3, as a mixedGalR1/GalR2 ligand has been implicated as a putative therapeutic for its potential effects,such as analgesic, anxiolytic and anticonvulsant effects (for a review see Mitsukawa et al.,2008 [5]). The peptide M1154retains high affinity binding toGalR2, although two fold lowerthan the published M1145(Ki 6.55 nM). M1154 binds withsimilar affinity to GalR1,disparate with the loss of affinitytowards GalR1 seen for M1145(Ki 587 nM). When tested onGalR3 M1154 showed nobinding at the highest testedconcentration, 10000 nM (Figure2). These results reveal thatM1154 is selective for GalR1 andFig. 2. Displacement curve for M1145 at hGalR1-3(n=3).GalR2 and the difference towardsGalR3 is greater than 1000 times;manuscript in preparation.AcknowledgmentsWe thank Kathryn A. Jones and Tiina P. Iismaa, Neurobiology Program, Garvan Institue of MedicalResearch, Sydney, Australia for Chinese Hamster Ovary cells stably transfected with Galanin Receptor2 and Silvia Gatti-McArthur and Monique Dellenbach, F. Hoffmann-La Roche AG, Basel, Switzerlandfor Flp-In T-REx 293 cell line stably transfected with the human GalR3. This work was supported bygrants from the Swedish Research Council (VR-MED), the Swedish Center for Biomembrane Reseach,the Knut and Alice Wallenberg Foundation, Stiftelsen Olle Engkvist Byggmästare (JR) andARCHIMEDES Foundation (IS).References1. Tatemoto, K., Rökaeus, A., Jörnvall, H., McDonald, T.J., Mutt, V. FEBS Lett. 164(1), 124-128(1983).2. Runesson, J., Robinson, J.K., Sollenberg, U.E., Langel, Ü. (2009). Twenty-five Years of GalaninResearch, in Bioactive Peptides Howl, J., Ed. CRC Press.3. Lu, X., Bartfai, T. Naunyn Schmiedbergs Arch. Pharmacol. 379(4), 417-420 (2009).4. Runesson, J., Saar, I., Lundström, L., Järv, J., Langel, Ü. Neuropeptides 43, 187-192 (2009).5. Mitsukawa, K., Lu, X., Bartfai, T. Cell. Mol. Life Sci. 65, 1796-805 (2008).453

Hooray! Your file is uploaded and ready to be published.

Saved successfully!

Ooh no, something went wrong!