Alkylboronic acids accelerate affinity labelling of acetylcholinesterase with N,N-dimethyl-2-phenylaziridinium ion.
The kinetics of acetylcholinesterase alkylation with N,N-dimethyl-2-phenylaziridinium ion, the anionic-site-directed affinity label, has been investigated in the presence of alkylboronic acids, which are known as the esteratic-site-directed reversible inhibitors of the enzyme. The ternary complex of the enzyme, the aziridinium ion and alkylboronic acid, are formed in this reaction. In the case of propylboronic acid, for which the complete kinetic analysis of the acceleration effect has been carried out, the 85-fold increase in the rate of the enzyme alkylation reaction has been found. This acceleration effect was connected with the alkylation step, whereas the non-covalent binding of the aziridinium ion in the enzyme active centre was even hindered by the alkylboronic acid. The possible mechanism of this kinetic acceleration phenomenon is discussed with special reference to the kinetic data for the spontaneous solvolysis reaction of the aziridinium ion in water and organic solvents.
D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D001388:Aziridines / Q000378:metabolism*; D001389:Azirines / Q000378:metabolism*; D001897:Boronic Acids / Q000494:pharmacology*; D004546:Elapid Venoms / Q000032:analysis; D007700:Kinetics
D001388:Aziridines; D001389:Azirines; D001897:Boronic Acids; D004546:Elapid Venoms; C001054:N,N-dimethyl-2-phenylaziridinium; D000110:Acetylcholinesterase