Hydrolytic reactions of cyclic bis(3′‐5′)diadenylic acid (c‐di‐AMP)

Hydrolytic reactions of cyclic bis(3′‐5′)diadenylic acid (c‐di‐AMP) have been followed by Reversed phase high performance liquid chromatography (RP‐HPLC) over a wide pH range at 90 °C. Under neutral and basic conditions (pH ≥ 7), disappearance of the starting material (first‐order in [OH − ]) was accompanied by formation of a mixture of adenosine 2′‐monophosphate and 3′‐monophosphate (2′‐AMP and 3′‐AMP). Under very acidic conditions (from H 0  = −0.7 to 0.2), c‐di‐AMP undergoes two parallel reactions (first‐order in [H + ]): the starting material is cleaved to 2′‐AMP and 3′‐AMP and depurinated to adenine (i.e., cleavage of the N ‐glycosidic bond), the former reaction being slightly faster than the latter one. At pH 1–3, isomerization to cyclic bis(2′‐5′)diadenylic acid competes with the depurination. Copyright © 2012 John Wiley & Sons, Ltd.