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

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

Research output: Contribution to journalArticlepeer-review

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 languageEnglish (US)
Pages (from-to)4177-4181
Number of pages5
JournalJournal of medicinal chemistry
Volume48
Issue number12
DOIs
StatePublished - Jun 16 2005

Fingerprint Dive into the research topics of 'Cyclic ADP-ribose analogues containing the methylenebisphosphonate linkage: Effect of pyrophosphate modifications on Ca<sup>2+</sup> release activity'. Together they form a unique fingerprint.

Cite this