Cyclic ADP-ribose analogues containing the methylenebisphosphonate linkage: effect of pyrophosphate modifications on Ca2+ release activity.
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[CH(2)]) and methylenebisphosphonate cyclic 3-deaza-ADP-ribose (3-deaza-cADPR[CH(2)]) showed full agonist activity for release of Ca(2+) ions from sea urchin egg homogenates. The EC(50) for cADPR[CH(2)] was 856 nM and that for 3-deaza-cADPR[CH(2)] was 300 nM, about 15- and 5-fold less potent than cADPR, respectively.
Xu
Libo
L
Department of Medicinal and Biological Chemistry, College of Pharmacy, The University of Toledo, Ohio 43606, USA.
Walseth
Timothy F
TF
Slama
James T
JT
D036541:ADP-ribosyl Cyclase / Q000737:chemistry; D000818:Animals; D001048:Aplysia; D002118:Calcium / Q000378:metabolism*; D002384:Catalysis; D036563:Cyclic ADP-Ribose / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004164:Diphosphonates / Q000737:chemistry*; D066298:In Vitro Techniques; D012617:Sea Urchins
D004164:Diphosphonates; C501766:methylenebisphosphonate cyclic 3-deaza-ADP-ribose; C501765:methylenebisphosphonate cyclic ADP-ribose; D036563:Cyclic ADP-Ribose; D036541:ADP-ribosyl Cyclase; D002118:Calcium