50(P-11) ミクロネシア産海綿より得られた興奮性アミノ酸および関連アミノ酸代謝物の研究(ポスター発表の部)

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Excitatory amino acids bind and activate ionotropic glutamate receptors (iGluR) in central nervous system (CNS). Since iGluR is a highly diverse class of the synaptic receptors both structurally and functionally, highly selective agonists and antagonists are in demand as tools to understand their roles in the CNS. Here, we report isolation, structure, and biological activities of excitatory amino acids and related compounds from sponges collected in the Micronesian waters. Dysidea herbacea collected in Yap state afforded isolations of neodysiherbaine A (2), a related compound of dysiherbaine (1), dysibetaine PP (3), dysibetaines CPa (4) and b(5). Compound 2 induced convulsion in mice when injected intracerebroventricular route with ED_<50> value of 16pmol/mouse. In radioligand binding assay 2 was shown to selectively displace labeled kainite and AMPA receptor ligands with IC_<50> values of 104±9.2,161±21nM, respectively. Dysibetaine PP (3) is a dipeptide betaine composed of N-methyl proline and pipecolic acid connected both by peptide bond and N,N-aminal linkage. Dysibetaines CPa (4) is a cyclopropane di-acid substituted with a (trimethylammonium)methyl group. Although 4 did not induce convulsion in mice, it showed moderate affinity both toward kinate and NMDA binding site with IC_<50> values of 13, 10μM, respectively. On the other hand 5 has affinity only toward KA binding site(IC_<50>=4.9±2.3μM). Spectral data indicated that planer structure of 5 corresponds with a mono-amide of 4. Determination of stereochemistry of 5 is now underway. Cribronic acid (2S, 4R, 5R)-4,5-dihydroxypipecolic acid-4-O-sulfate, 6) is isolated from a Palauan sponge Cribrochalina olemda as a potent convulsant in mice. On thither hand, (2S, 4S)-4-hydroxypipecolic acid-4-O-sulfate (7) was isolated as a common convulsant of Axinella carteri and Stylotella aurantium. Both 6 and 7 selectively displaced labeled NMDA ligand in the radioligand binding assay.
天然有機化合物討論会の論文
2002-09-01

50(P-11) ミクロネシア産海綿より得られた興奮性アミノ酸および関連アミノ酸代謝物の研究(ポスター発表の部)

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