Nicotinic acid adenine dinucleotide phosphate analogues containing substituted nicotinic acid: Effect of modification on Ca2+ release

Pooja Jain, James T. Slama, Leroy A. Perez-Haddock, Timothy F Walseth

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Analogues of nicotinic acid adenine dinucleotide phosphate (NAADP) with substitution at either the 4- or the 5-position position of the nicotinic acid moiety have been synthesized from NADP enzymatically using Aplysia californica ADP-ribosyl cyclase or mammalian NAD glycohydrolase. Substitution at the 4-position of the nicotinic acid resulted in the loss of agonist potency for release of Ca2+-ions from sea urchin egg homogenates and in potency for competition ligand binding assays using [32P]NAADP. In contrast, several 5-substituted NAADP derivatives showed high potency for binding and full agonist activity for Ca2+ release. 5-Azido-NAADP was shown to release calcium from sea urchin egg homogenates at low concentration and to compete with [32P]NAADP in a competition ligand binding assay with an IC50 of 18 nM, indicating that this compound might be a potential photoprobe useful for specific labeling and identification of the NAADP receptor.

Original languageEnglish (US)
Pages (from-to)7599-7612
Number of pages14
JournalJournal of medicinal chemistry
Volume53
Issue number21
DOIs
StatePublished - Nov 11 2010

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