Neurotoxin Mitigation
Abstract
Organophosphorus esters (OP) are highly toxic poisons used as chemical nerve agents and as pesticides. It is generally agreed that the toxicity from high dose OP exposure involves inhibition of acetyl cholinesterase. The role of other proteins in the toxicity of OP is unknown. Our hypothesis is that several proteins become modified after exposure to OP and that the biological actions of OP are not explained by inhibition of acetylcholinesterase alone. We are using mass spectrometry to identify proteins modified by exposure to OP. A new motif for OP binding is beginning to emerge from our work. We are seeing a pattern of covalent OP binding to tyrosine where the tyrosine is adjacent to an arginine or lysine. We have identified tyrosine 411 on the surface of human albumin and tyrosine 238 of human transferrin as OP-binding sites. Our results are relevant to diagnosis of OP exposure. The mass spectrometry methods we have developed are rapid and simple, but expensive. The new information from our mass spectrometry results can be used to develop antibody based dipstick assays to diagnose OP exposure.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 2007
- Accession Number
- ADA476755
Entities
People
- Steven H. Hinrichs
Organizations
- University of Nebraska Medical Center