64 テトロドトキシンの誘導体の調製とNa^+チャンネル結合活性の測定(ポスター発表の部)

概要

論文の詳細を見る
Twelve derivatives of tetrodotoxin (TTX, 1) were prepared and determined of their binding potencies to Na^+ channels. 4-EpiTTX (2), 6-epiTTX (3), 11-deoxyTTX (4), chiriquitoxin (10) and 4,9-anhydroTTX (12) were isolated from the natural sources. 11-OxoTTX (5), 11-norTTX-6,6-diol (6), 11-norTTX-6(S)-ol (7), 11-norTTX-6(R)-ol (8), TTX-11-carboxylic acid (9), and TTX-8-O-hemisuccinate (11), and tetrodonic acid (13) were chemically prepared from 1. Isolation, chemical reaction and purities of the final products were monitored by a highly-sensitive fluorometric HPLC analyzer constructed by us. The quantity of each derivative was determined by ^1H NMR spectroscopy by comparing the signal intensity of H4 with that of t-BuOH added to the solvent as an inner standard. Purities of the derivatives were proved to be more than 99.3% by HPLC analyses. Their binding potencies to the Na^+ channel protein were determined by competitive binding assays against ^3H-saxitoxin, which shares the same binding site with 1. 5, 6, and 10 retained the high potency of 1. The potencies of 2, 3, 4, 7 and 8 were decreased to 1/20-1/40 of 1. Moreover, the channel binding potency was almost lost in 9, 11, 12, 13. Those results supported the stereostructural locations of charged amino acid groups around the binding site of 1 deduced from the site-directed mutagenesis and the photoaffinity labeling experiments of the Na^+ channel.
天然有機化合物討論会の論文
1993-09-10