Activation of IP3 receptors by synthetic bisphosphate ligands

Kana M. Sureshan, Andrew M. Riley, Ana M. Rossi, Stephen C. Tovey, Skarlatos G. Dedos, Colin W. Taylor, Barry V. L. Potter

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Abstract

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.
Original languageEnglish
Pages (from-to)1204-1206
JournalChemical Communications
Volume2009
Issue number10
Early online date4 Feb 2009
DOIs
Publication statusPublished - 14 Mar 2009

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Sureshan, K. M., Riley, A. M., Rossi, A. M., Tovey, S. C., Dedos, S. G., Taylor, C. W., & Potter, B. V. L. (2009). Activation of IP3 receptors by synthetic bisphosphate ligands. Chemical Communications, 2009(10), 1204-1206. https://doi.org/10.1039/b819328b