TY - JOUR
T1 - Cyclic 3-deaza-adenosine diphosphoribose
T2 - a potent and stable analog of cyclic ADP-ribose
AU - Wong, Long
AU - Aarhus, Robert
AU - Cheung Lee, Hon
AU - Walseth, Timothy F.
N1 - Funding Information:
We would like to thank Dr. Richard Graeff for assistance with assays using the 96-well fluorescence plate reader, Dr. Cyrus Munshi for providing recombinant CD38 and Dr. Deborah Dickey for many helpful discussions. This work was funded by grants from NIH (DA11806) and the Minnesota Medical Foundation to T.F.W. and NIH (HD17484) to H.C.L.
PY - 1999/11/16
Y1 - 1999/11/16
N2 - Cyclic 3-deaza-adenosine diphosphoribose (3-deaza-cADPR), an analog of cyclic adenosine diphosphoribose (cADPR) was synthesized. 3-deaza-cADPR differs from cADPR by only the substitution of carbon for nitrogen at the 3-position of the purine ring. Similar to cADPR, the analog has potent calcium releasing activity in sea urchin egg homogenates and was able to induce calcium release at concentrations as low as 0.3 nM. The EC50 value for 3-deaza-cADPR-induced calcium release was 1 nM, which is about 70 times more potent than cADPR. The properties of calcium release induced by 3-deaza-cADPR in all other respects were similar to those of cADPR. Thus, 3-deaza-cADPR and cADPR were capable of cross-desensitizing each other and their calcium releasing activities were potentiated by Sr2+ as well as caffeine. 8-amino-cADPR, a selective antagonist of cADPR, was also able to inhibit 3-deaza-cADPR induced calcium release. Taken together, these data suggest that 3-deaza-cADPR releases calcium through the same mechanism as cADPR. 3-deaza-cADPR was found to be resistant to both heat and enzymatic hydrolysis. Only 15% of 3-deaza-cADPR was destroyed after boiling this compound for 2 h. No loss of 3-deaza-cADPR was observed when treated with CD38 under conditions where cADPR was completely hydrolyzed. Thus, 3-deaza-cADPR is a potent and stable analog of cADPR. These properties should make 3-deaza-cADPR a useful probe in studies focused on the mechanism of cADPR action. Copyright (C) 1999 Elsevier Science B.V.
AB - Cyclic 3-deaza-adenosine diphosphoribose (3-deaza-cADPR), an analog of cyclic adenosine diphosphoribose (cADPR) was synthesized. 3-deaza-cADPR differs from cADPR by only the substitution of carbon for nitrogen at the 3-position of the purine ring. Similar to cADPR, the analog has potent calcium releasing activity in sea urchin egg homogenates and was able to induce calcium release at concentrations as low as 0.3 nM. The EC50 value for 3-deaza-cADPR-induced calcium release was 1 nM, which is about 70 times more potent than cADPR. The properties of calcium release induced by 3-deaza-cADPR in all other respects were similar to those of cADPR. Thus, 3-deaza-cADPR and cADPR were capable of cross-desensitizing each other and their calcium releasing activities were potentiated by Sr2+ as well as caffeine. 8-amino-cADPR, a selective antagonist of cADPR, was also able to inhibit 3-deaza-cADPR induced calcium release. Taken together, these data suggest that 3-deaza-cADPR releases calcium through the same mechanism as cADPR. 3-deaza-cADPR was found to be resistant to both heat and enzymatic hydrolysis. Only 15% of 3-deaza-cADPR was destroyed after boiling this compound for 2 h. No loss of 3-deaza-cADPR was observed when treated with CD38 under conditions where cADPR was completely hydrolyzed. Thus, 3-deaza-cADPR is a potent and stable analog of cADPR. These properties should make 3-deaza-cADPR a useful probe in studies focused on the mechanism of cADPR action. Copyright (C) 1999 Elsevier Science B.V.
KW - 3-deaza-cyclic ADP-ribose
KW - Calcium release
KW - Cyclic ADP-ribose
KW - cADPR
UR - http://www.scopus.com/inward/record.url?scp=0032749886&partnerID=8YFLogxK
U2 - 10.1016/S0304-4165(99)00161-0
DO - 10.1016/S0304-4165(99)00161-0
M3 - Article
C2 - 10564770
AN - SCOPUS:0032749886
SN - 0304-4165
VL - 1472
SP - 555
EP - 564
JO - Biochimica et Biophysica Acta - General Subjects
JF - Biochimica et Biophysica Acta - General Subjects
IS - 3
ER -