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Chem Commun (Camb). 2009 Mar 14;(10):1204-6. doi: 10.1039/b819328b. Epub 2009 Feb 4.

Activation of IP(3) receptors by synthetic bisphosphate ligands.

Author information

1
Wolfson Laboratory of Medicinal Chemistry, Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, UK Bath BA2 7AY.

Abstract

Ca(2+) 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 IP(3), 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 IP(3)R without a vicinal bisphosphate motif; this will stimulate new approaches to IP(3)R ligand design.

PMID:
19240874
PMCID:
PMC2898634
DOI:
10.1039/b819328b
[Indexed for MEDLINE]
Free PMC Article

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