Moreau C , Ashamu GA , Bailey VC , Galione A , Guse AH , Potter BV .

084068 Wellcome Trust , Medical Research Council , Wellcome Trust

	Fig. 1. cADPR analogue structures and numbering system.
	Scheme 1. Synthesis of 8-modified cADPR analogues. Reagents and conditions: (a) PdCl2, PPh3, AlMe3, THF, reflux, 2.5 h. (b) POCl3, TEP, 0 °C. (c) β-NMN+, DCC, pyridine:water (4 : 1), 7 days, rt. (d) Aplysia cyclase, 25 mM HEPES (pH 6.8), 20 min, rt.
	Scheme 2. Synthesis of cAcycloDPR. Reagents and conditions: (a) POCl3, TEP, 0 °C, 1.5 h then ice/water. (b) β-NMN+, DCC, 7 days, rt. (c) Aplysia cyclase, 25 mM HEPES (pH 6.8), rt.
	Scheme 3. Synthesis of cAraDPR. Reagents and conditions: (a) POCl3, TEP, 0 °C, 1.5 h then ice/water. (b) β-NMN+, DCC, 7 days, rt. (c) Aplysia cyclase, 25 mM HEPES (pH 6.8), rt.
	Scheme 4. Synthesis of cAcetDPR. Reagents and conditions: (a) POCl3, TEP, 0 °C, 1.5 h then ice/water. (b) β-NMN+, DCC, 7 days, rt. (c) Aplysia cyclase, 25 mM HEPES (pH 6.8), rt.
	Fig. 2. Tautomeric form of 8-“hydroxyl” AMP (26a) vs. 8-oxy AMP (26b).
	Fig. 3. Schematic representation of the ribofuranose ring in both C2′ endo and C3′ endo conformation.
	Fig. 4. Structures of the cADPR analogues mentioned herein – our group.
	Fig. 5. Structures of the cADPR analogues mentioned herein – Shuto's group.
	Fig. 6. Model of 8-Br cADPR (2) with its “southern” ribose in the C2′ endo/syn conformation. Hydrogen atoms are not shown for clarity.

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