Journal
CHEMICAL COMMUNICATIONS
Volume -, Issue 10, Pages 1204-1206Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/b819328b
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Funding
- Wellcome Trust [082837, 072084]
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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.
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