11-OXO-TETRODOTOXIN AND A SPECIFICALLY LABELLED H-3-TETRODOTOXIN

摘要

Tetrodotoxin was oxidized to a hydrated aldehyde, 11-oxo-tetrodotoxin, which shares the specificity of tetrodotoxin for the Na+ channel of the isolated voltage-clamped frog skeletal muscle fiber, but is four to five times more potent. It binds to the solubilized Na+ channel of eel electroplax with a similarly higher potency, because of an equilibrium dissociation constant about 0.25, and a dissociation rate constant 2.4 times slower than those for tetrodotoxin. 11-Oxo-tetrodotoxin can be reduced to regenerate a tetrodotoxin, which is chemically and biologically indistinguishable from the original tetrodotoxin. By reducing with tritiated sodium borohydride, a H-3 marker can be inserted regiospecifically to yield 11-[H-3]-tetrodotoxin. Because it has a defined specific activity of >2.5 Ci/mmole, and a H-3 marker which does not exchange with solvent proton, 11-[H-3]-tetrodotoxin is an ideal tracer for tetrodotoxin. It may enable studies of problems which require higher signals and/or better stability of the marker than those obtainable from currently available tracer Na+-channel ligands. (C) 1996 Elsevier Science Ltd. [References: 21]