Synthesis and use of cell-permeant cyclic ADP-ribose

Endoplasmic reticulum and lysosomal Ca2+ stores are remodelled in GBA1-linked Parkinson disease patient fibroblasts

“…S1A ). To further examine ER Ca 2+ release, fibroblasts were stimulated with a cell-permeable derivative of the intracellular Ca 2+ -mobilising messenger cyclic-ADP ribose (cADPR-AM) [23] . cADPR-AM (25 μM) evoked Ca 2+ signals in a proportion of fibroblasts ( Fig.…”

“…Ca 2+ imaging was performed using the fluorescent Ca 2+ indicator Fura-2 as described in [6] using HEPES-buffered saline (HBS) consisting of 10 mM HEPES, 2 mM MgSO 4 , 156 mM NaCl, 3 mM KCl, 2 mM CaCl 2 , 1.25 mM KH 2 PO 4 and 10 mM glucose (pH 7.4). Cells were stimulated with thapsigargin (Merck), cADPR-AM, synthesised as described previously [23] and GPN (glycyl- l -phenylalanine 2-naphthylamide, SantaCruz Biotech). Where indicated, extracellular Ca 2+ was replaced with 1 mM EGTA.…”

Roles and mechanisms of the CD38/cyclic adenosine diphosphate ribose/Ca2+signaling pathway

“…Later, Lee et al [5] solved the structure of cADPR by x-ray crystallography and showed that it is a novel cyclic nucleotide formed by the covalent linkage of the N1 nitrogen of the adenine ring to the anomeric carbon of the terminal ribose to become a closed cyclic structure (Figure 2). Benefiting from the identified structure, multiple cADPR analogs have been synthesized, which greatly promoted research on the role and mechanism of cADPR-mediated Ca 2+ signaling [6][7][8][9] . From the very beginning of research on cADPR, several pharmacological studies have clearly shown that the mechanism of cADPR-induced Ca 2+ release is different from that of IP3.…”

New Linear Precursors of cIDPR Derivatives as Stable Analogs of cADPR: A Potent Second Messenger with Ca2+-Modulating Activity Isolated from Sea Urchin Eggs

“…The latter is able also to catalyze the inverse hydrolytic reaction that produces adenosine diphosphate ribose (ADPR) [17]. The physiological instability of cADPR at the N1-glycosidic bond [17], together with its low ability to cross membranes, likely for the presence of the negative charge at the pyrophosphate moiety [18], have prompted some researchers to develop semi-synthetic and/or synthetic methodologies to obtain novel non-hydrolysable and cell permeant analogues [17,19,20,21,22,23].…”

“…Over the last years, our research group synthesized several cIDPR analogues [30,31,32,33,34,35,36,37]. In particular, the pyrophosphate (cpIDP, 3 , Figure 1) [30] and the monophosphate (cpIMP, 4 , Figure 1) [36] derivatives with a pentyl chain replacing the “northern” ribose showed interesting Ca 2+ -releasing activities in PC12 cells differentiated in neurons with the use of nerve growth factor (NGF) [18]. Meanwhile, the pyrophosphate derivative with a butyl chain in the place of the “northern” ribose was inactive on the same cell line [37].…”