Molecular Probe Analysis of Mammalian Brain Acetylcholinesterase
Abstract
During the project period covered by this contract, our work emphasized studies of the kinetic properties of purified bovine brain acetylcholinesterase (AChE) and experiments to chemically modify the reactivity of this enzyme. Our goal has been to define the properties of peripheral or extra-catalytic sites on AChE in the hope that chemical modification of organophosphate (OP) inhibition can be achieved through binding at the peripheral sites. It is expected that susceptibility to OP inhibition can be reduced while maintaining the enzyme's catalytic activity. Among the peripheral site ligands studied, tetrahydroaminoacridine and lucanthone provided the most promising evidence of pharmacological modification. In addition, a number of non-pharmacological compounds, i.e., nonselective and quite neurotoxic compounds, such as the water-soluble carbodiimides and phenylglyoxal (an arginine group ligand), also reduced AChE susceptibility to certain phosphorylating inhibitors. Keywords: Acetylcholinesterase, Organophosphates, Neurotoxicity, Chemical modification, Tetrahydroaminoacridine.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 27, 1988
- Accession Number
- ADA201735
Entities
People
- Judith K. Marquis
Organizations
- Boston University