ADENOPHOSTIN-A AND ADENOPHOSTIN-B - POTENT AGONISTS OF INOSITOL-1,4,5-TRISPHOSPHATE RECEPTOR PRODUCED BY PENICILLIUM-BREVICOMPACTUM STRUCTURE ELUCIDATION

Adenophostins A (1, C16H26N5O18P3) and B (2, C18H28N5O19P3), potent agonists of inositol-1,4,5-trisphosphate (InsP(3)) 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 a-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 InsP, itself for binding to the InsP, receptor were 0.18 nbr, 0.18 nM, 0.29 nM and 15 nM, respectively.