Adenophostins A and B: Potent agonists of inositol-1,4,5-trisphosphate receptor produced by Penicillium brevicompactum: Structure elucidation

Article abstract of DOI:10.7164/antibiotics.47.95

Adenophostins A (1, C₁₆H₂₆N₅O₁₈P₃) and B (2, C₁₈H₂₈N₅O₁₉P₃), potent agonists of inositol-1,4,5-trisphosphate (InsP₃) receptor, were isolated from the culture broths of Penicillium brevicompactum SANK 11991 and SANK 12177. Hydrolysis of 2 with aq NaOH gave 1. Oxidation of 2 with NaNO₂ gave the hypoxanthine derivative (3). Treatment of 1 or 2 with alkaline phosphatase gave 4 and 5. Treatment of 4 with α-glucosidase gave adenosine. Thus, their structures were deduced to be adenosine nucleotides by NMR, MS and the enzymatic degradation. The inhibitory constants (Ki value) of 1, 2, 3 and InsP₃ itself for binding to the InsP₃ receptor were 0.18 nM, 0.18 nM, 0.29 nM and 15nM, respectively.