Adenophostins A and 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-triphosphate (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 alpha-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 15 nM, respectively.
Takahashi
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Fermentation Research Laboratories, Sankyo Co., Ltd., Tokyo, Japan.
Kinoshita
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Takahashi
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D000241:Adenosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D006868:Hydrolysis; D053496:Inositol 1,4,5-Trisphosphate Receptors; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D010407:Penicillium / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects* / Q000378:metabolism
D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear; C085029:adenophostin A; C085030:adenophostin B; D000241:Adenosine