Cyclic ADP-ribose analogues containing the methylenebisphosphonate linkage: Effect of pyrophosphate modifications on Ca2+ release activity

Libo Xu; Timothy F. Walseth; James T. Slama

doi:10.1021/jm049469l

Cyclic ADP-ribose analogues containing the methylenebisphosphonate linkage: Effect of pyrophosphate modifications on Ca²⁺ release activity

Libo Xu, Timothy F. Walseth, James T. Slama

Pharmacology

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21 Scopus citations

Abstract

Analogues of cyclic ADP-ribose (cADPR) incorporating a methylenebisphosphonate linkage in the place of the pyrophosphate have been synthesized from nicotinamide adenine dinucleotide analogues enzymatically using Aplysia californica ADP-ribosyl cyclase. Methylenebisphosphonate cyclic ADP-ribose (CADPR[CH₂]) and methylenebisphosphonate cyclic 3-deaza-ADP-ribose (3-deaza-cADPR[CH₂]) showed full agonist activity for release of Ca²⁺ ions from sea urchin egg homogenates. The EC ₅₀ for cADPR [CH₂] was 856 nM and that for 3-deaza-cADPR [CH₂] was 300 nM, about 15- and 5-fold less potent than cADPR, respectively.

Original language	English (US)
Pages (from-to)	4177-4181
Number of pages	5
Journal	Journal of medicinal chemistry
Volume	48
Issue number	12
DOIs	https://doi.org/10.1021/jm049469l
State	Published - Jun 16 2005

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title = "Cyclic ADP-ribose analogues containing the methylenebisphosphonate linkage: Effect of pyrophosphate modifications on Ca2+ release activity",

abstract = "Analogues of cyclic ADP-ribose (cADPR) incorporating a methylenebisphosphonate linkage in the place of the pyrophosphate have been synthesized from nicotinamide adenine dinucleotide analogues enzymatically using Aplysia californica ADP-ribosyl cyclase. Methylenebisphosphonate cyclic ADP-ribose (CADPR[CH2]) and methylenebisphosphonate cyclic 3-deaza-ADP-ribose (3-deaza-cADPR[CH2]) showed full agonist activity for release of Ca2+ ions from sea urchin egg homogenates. The EC 50 for cADPR [CH2] was 856 nM and that for 3-deaza-cADPR [CH2] was 300 nM, about 15- and 5-fold less potent than cADPR, respectively.",

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AU - Walseth, Timothy F.

AU - Slama, James T.

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AB - Analogues of cyclic ADP-ribose (cADPR) incorporating a methylenebisphosphonate linkage in the place of the pyrophosphate have been synthesized from nicotinamide adenine dinucleotide analogues enzymatically using Aplysia californica ADP-ribosyl cyclase. Methylenebisphosphonate cyclic ADP-ribose (CADPR[CH2]) and methylenebisphosphonate cyclic 3-deaza-ADP-ribose (3-deaza-cADPR[CH2]) showed full agonist activity for release of Ca2+ ions from sea urchin egg homogenates. The EC 50 for cADPR [CH2] was 856 nM and that for 3-deaza-cADPR [CH2] was 300 nM, about 15- and 5-fold less potent than cADPR, respectively.

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Cyclic ADP-ribose analogues containing the methylenebisphosphonate linkage: Effect of pyrophosphate modifications on Ca²⁺ release activity

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