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

J Antibiot (Tokyo). 1994 Jan;47(1):95-100. doi: 10.7164/antibiotics.47.95.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / chemistry
  • Adenosine / metabolism
  • Adenosine / pharmacology
  • Calcium Channels / drug effects*
  • Calcium Channels / metabolism
  • Hydrolysis
  • Inositol 1,4,5-Trisphosphate Receptors
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Penicillium / metabolism
  • Receptors, Cytoplasmic and Nuclear / drug effects*
  • Receptors, Cytoplasmic and Nuclear / metabolism

Substances

  • Calcium Channels
  • Inositol 1,4,5-Trisphosphate Receptors
  • Receptors, Cytoplasmic and Nuclear
  • adenophostin A
  • adenophostin B
  • Adenosine