Clostridial Modified Toxins Containing an Integrated Site-Binding Protease Cleavage Domain

摘要

1. A single-chain modified Clostridial toxin containing: a) the enzyme domain of the Clostridial toxin capable of performing the enzyme directed modification stage of the Clostridial toxin process; b) the translocation domain of the Clostridial toxin capable of performing the translocation stage of the Clostridial toxin process; and c) an integrated protease cleavage site-binding domain containing the P portion of the protease cleavage site, including the P site of the unstable chemical bond and a binding domain, the P site of the protease cleavage site adjacent to the amino terminus of the binding domain, thereby creating an integrated protease cleavage site; where cleavage of the integrated site-binding domain of the protease cleavage converts the single-chain modified Clostridial toxin into a double-stranded form and forms a binding domain with an amino end capable of binding to its cognate receptor. 2. The modified Clostridial toxin according to claim 1, characterized in that the modified Clostridial toxin contains a linear amino carboxyl single polypeptide order of 1) the enzyme domain of the Clostridial toxin, the translocation domain of the Clostridial toxin and the integrated site-binding domain of the protease cleavage, 2) the enzyme domain of the Clostridial toxin integrated site-binding domain of protease cleavage and translocation domain of the toxin Clostridial, 3) integrated site-binding domain of protease cleavage, translocation the domain of the Clostridial toxin and the enzyme domain of the Clostridial toxin, 4) an integrated site-binding domain of protease cleavage, the current enzyme domain