A Minimal Structural Analogue of Cyclic ADP-ribose

2′-Deoxy Cyclic Adenosine 5′-Diphosphate Ribose Derivatives: Importance of the 2′-Hydroxyl Motif for the Antagonistic Activity of 8-Substituted cADPR Derivatives

“…42 This compound however only works efficiently in the T lymphocyte but not in the SUH system. Zhang et al 19,20 reported that replacement of the ribose moiety with an ether bridge could lead to promising membrane-permeant agents, but these compounds are still only weak agonists. 8-bromo-N1-cIDPR was also found to be a cell-permeant agonist in T-lymphocytes, but the agonistic effect was also weak.…”

“…More importantly, it is not known what conformation cADPR analogues may adopt when they actually bind to their receptor. Other work 19,20 explored radical structural modifications of the northern ribose in particular, but only agonistic activities were observed. Modification of the pyrophosphate system led to potent agonist activity for a triphosphate analogue of cADPR, 21 and phosphonate analogues showed decreased agonist activity.…”

Cyclic ADP‐Ribose Analogues with Minimal Structure: Synthesis and Calcium‐Release Activity

“…Comparison of the calcium-release activities of cIDPRE and cADPR revealed that the greater flexibility of the whole molecule introduced by replacement of the northern ribose by the ether strand either still allows fitting into the binding site or allows the functional groups to support a conformation much more like cADPR. Because of the same structure of the northern and southern ribose occurring (Guse et al, 2005). The key steps for the synthesis of cIDP-DE include the synthesis of the N 9 -substituted hypoxanthine (Scheme 8.5) and the intramolecular cyclization of the bisphosphate intermediate (Scheme 8.6).…”

Nicotinamide Benzimidazolide Dinucleotides, Non-Cyclisable Analogues of NAD+

“…[10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] The synthesis of cADPR analogues (2-18; Figure 1) from novel nucleoside precursors has been achieved using either a total chemical route or a chemoenzymatic approach. [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] The chemical route is mostly used to access cADPR analogues unattainable through enzymatic cyclisation reactions. 22,26 The chemoenzymatic approach to cADPR derivatives is based on the chemical synthesis of NAD + analogues followed by an enzymatic cyclisation using the commercially available adenosine diphosphoribosyl cyclase isolated from Aplysia californica (ADPRC).…”

“…[10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] The chemical route is mostly used to access cADPR analogues unattainable through enzymatic cyclisation reactions. 22,26 The chemoenzymatic approach to cADPR derivatives is based on the chemical synthesis of NAD + analogues followed by an enzymatic cyclisation using the commercially available adenosine diphosphoribosyl cyclase isolated from Aplysia californica (ADPRC). This approach is facilitated by the fact that this latter enzyme has high cyclase activity and low substrate specificity.…”