Activation of IP3 receptors by synthetic bisphosphate ligands
Sureshan, K. M., Riley, A. M., Rossi, A. M., Tovey, S. C., Dedos, S. G., Taylor, C. W. and Potter, B. V. L., 2009. Activation of IP3 receptors by synthetic bisphosphate ligands. Chemical Communications
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Ca2+ release by D-myo-inositol 1,4,5-trisphosphate receptors (IP(3)Rs) is widely considered to require the vicinal 4,5-bisphosphate motif of IP3, with P-5 and P-4 engaging the alpha and beta domains of the binding site; using synthesis and mutagenesis we show that the adenine of synthetic glyconucleotides, through an interaction with Arg504, can replace the interaction of either P-1 or P-5 with the alpha-domain producing, respectively, the most potent bisphosphate agonist yet synthesised and the first agonist of IP3R without a vicinal bisphosphate motif; this will stimulate new approaches to IP3R ligand design.
|Creators||Sureshan, K. M., Riley, A. M., Rossi, A. M., Tovey, S. C., Dedos, S. G., Taylor, C. W. and Potter, B. V. L.|
|Departments||Faculty of Science > Pharmacy & Pharmacology|
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