Design and Production of an Organophosphorus-Bioscavenger via Protein Engineering of the Human Acetylcholinesterase
Final rept. 1 Jun 2000-31 Aug 2002
ISRAEL INST FOR BIOLOGICAL RESEARCH NESS ZIONA
Pagination or Media Count:
The design of novel biocatalysts with potential pharmacological use against organophosphate OP poisoning, within the mold of recombinant human acetyicholinesterase rHuAChE, was carried out by two complementing research approaches a. Kinetic studies combined with mass spectrometric analysis of rHuAChE and selected mutants thereof, with a variety of OPs for better understanding of the chemical environment for the OPs in the active center of AChE. Specifically, here we describe the effects of multiple replacements of aromatic residues at the active center on reactivity toward OP agents, as well as report on the resolution of some of the less understood reaction pathways of phosphylation, and aging involving phosphoroamidates P-N agents such as tabun and butyl-tabun. b. Analyses of post-translation modifications responsible for the limited residence time of rHuAChE Extensive structural analysis of the N-glycans of recombinant bovine and human AChE and native bovine AChE, identified specific termini that account for the observed differential behavior of the recombinant and native enzymes.
- Organic Chemistry
- Chemical, Biological and Radiological Warfare