Synthesis of New, Highly Radioactive Tetrodotoxin Derivatives and Their Binding Properties to the Sodium Channel

Abstract

The Pfitzner-Moffatt oxidation procedure was used to prepare 5 derivatives of tetrodotoxin by covalent attachment of the oxidized toxin to Lys, Gly, .beta.-alanine or ethylenediamine. These derivatives reach specific radioactivities between 5 and 45 Ci/mmol. The equilibrium properties of binding of these tetrodotoxin derivatives to membrane-embedded or solubilized Na channels from crustacean [Carcinus maenas] nerves were analysed and compared to the binding properties of tritiated tetrodotoxin and saxitoxin to the same biological systems. All these highly radiolabeled derivatives associate to the tetrodotoxin binding component with properties similar to those of tetrodotoxin itself. The synthetic route described in this paper may be used to prepare other types of tetrodotoxin derivatives such as fluorescent derivatives.